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  • 1.
    Ahlm, Clas
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Linderholm, M
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Alexeyev, O A
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Billheden, J
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Fagerlund, M
    Zetterlund, B
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neurophysiology.
    Settergren, B
    Central nervous system and ophthalmic involvement in nephropathia epidemica (European type of haemorrhagic fever with renal syndrome)1998In: Journal of Infection, ISSN 0163-4453, E-ISSN 1532-2742, Vol. 36, no 2, p. 149-155Article in journal (Refereed)
    Abstract [en]

    Central nervous system (CNS) - related symptoms occur in haemorrhagic fever with renal syndrome (HFRS). To study the CNS and ophthalmic involvement in nephropathia epidemica (NE), the European type of HFRS, we included 26 patients in a prospective study. Most common CNS-related symptoms were headache (96%), insomnia (83%), vertigo (79%), nausea (79%), and vomiting (71%). Ophthalmic symptoms were reported by 82% of patients; 41% had photophobia and 50% had impaired vision. A transient loss of vision was recorded in one patient, who also had a generalized seizure. Minor white matter lesions were found in about half of the patients investigated with brain magnetic resonance imaging (MRI). Electroencephalography (EEG) showed severe alterations in only one patient, and slight and reversible patterns in another two patients. Neopterin, interleukin-6 and interferon-gamma levels in the cerebrospinal fluid (CSF) were elevated, which may indicate immune activation. However, we found no evidence of intrathecal NE virus replication. We conclude that CNS-related symptoms are common in NE, and transient ophthalmic involvement can be demonstrated in about half of the patients.

  • 2.
    Ahmadi, Mahboobah
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Liu, Jing-Xia
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Brännström, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Andersen, Peter M
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Pedrosa-Domellöf, Fatima
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Human extraocular muscles in ALS2010In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 51, no 7, p. 3494-3501Article in journal (Refereed)
    Abstract [en]

    PURPOSE. To investigate the general morphology, fiber type content, and myosin heavy chain (MyHC) composition of extraocular muscles (EOMs) from postmortem donors with amyotrophic lateral sclerosis (ALS) and to evaluate whether EOMs are affected or truly spared in this disease. METHODS. EOM and limb muscle samples obtained at autopsy from ALS donors and EOM samples from four control donors were processed for immunohistochemistry with monoclonal antibodies against distinct MyHC isoforms and analyzed by SDS-PAGE. In addition, hematoxylin and eosin staining and nicotinamide tetrazolium reductase (NADH-TR) activity were studied. RESULTS. Wide heterogeneity was observed in the appearance of the different EOMs from each single donor and between donors, irrespective of ALS type or onset. Pathologic morphologic findings in ALS EOMs included presence of atrophic and hypertrophic fibers, either clustered in groups or scattered; increased amounts of connective tissue; and areas of fatty replacement. The population of fibers stained with anti-MyHCslow tonic was smaller than that of MyHCIpositive fibers and was mostly located in the orbital layer in most of the ALS EOM samples, whereas an identical staining pattern for both fiber populations was observed in the control specimens. MyHCembryonic was notably absent from the ALS EOMs. CONCLUSIONS. The EOMs showed signs of involvement with altered fiber type composition, contractile protein content, and cellular architecture. However, when compared to the limb muscles, the EOMs were remarkably preserved. EOMs are a useful model for the study of the pathophysiology of ALS.

  • 3.
    Alm, Albert
    et al.
    Ögonkliniken, Akademiska sjukhuset, Uppsala .
    Bengtsson, Boel
    Oftalmologi, SUS, Malmö.
    Calissendorff, Berit
    St Eriks ögonsjukhus, Stockholm.
    Eckerlund, Ingemar
    Swedish Council on Technology Assessment in Health Care, Stockholm.
    Heijl, Anders
    Department of Clinical Sciences, Ophthalmology in Malmö.
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Öppenvinkelglaukom (grön starr): diagnostik, uppföljning och behandling. En systematisk litteraturöversikt.2008Report (Other academic)
  • 4.
    Ambarki, Khalid
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Hallberg, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Jóhannesson, Gauti
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Zarrinkoob, Laleh
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Wåhlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Birgander, Richard
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Blood flow of ophthalmic artery in healthy individuals determined by phase-contrast magnetic resonance imaging2013In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 54, no 4, p. 2738-2745Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Recent development of magnetic resonance imaging (MRI) offers new possibilities to assess ocular blood flow. This prospective study evaluates the feasibility of phase-contrast MRI (PCMRI) to measure flow rate in the ophthalmic artery (OA) and establish reference values in healthy young (HY) and elderly (HE) subjects.

    METHODS: Fifty HY subjects (28 females, 21-30 years of age) and 44 HE (23 females, 64-80 years of age) were scanned on a 3-Tesla MR system. The PCMRI sequence had a spatial resolution of 0.35 mm per pixel, with the measurement plan placed perpendicularly to the OA. Mean flow rate (Qmean), resistive index (RI), and arterial volume pulsatility of OA (ΔVmax) were measured from the flow rate curve. Accuracy of PCMRI measures was investigated using a vessel-phantom mimicking the diameter and the flow rate range of the human OA.

    RESULTS: Flow rate could be assessed in 97% of the OAs. Phantom investigations showed good agreement between the reference and PCMRI measurements with an error of <7%. No statistical difference was found in Qmean between HY and HE individuals (HY: mean ± SD = 10.37 ± 4.45 mL/min; HE: 10.81 ± 5.15 mL/min, P = 0.655). The mean of ΔVmax (HY: 18.70 ± 7.24 μL; HE: 26.27 ± 12.59 μL, P < 0.001) and RI (HY: 0.62 ± 0.08; HE: 0.67 ± 0.1, P = 0.012) were significantly different between HY and HE.

    CONCLUSIONS: This study demonstrated that the flow rate of OA can be quantified using PCMRI. There was an age difference in the pulsatility parameters; however, the mean flow rate appeared independent of age. The primary difference in flow curves between HE and HY was in the relaxation phase of the systolic peak.

  • 5. Anjos, Rita
    et al.
    Vieira, Luisa
    Costa, Livio
    Vicente, André
    Ophthalmology Department, Centro Hospitalar de Lisboa Central, Lisbon, Portugal; Serviço de Oftalmologia, Hospital de Santo António dos Capuchos, Lisbon, Portugal.
    Santos, Arnaldo
    Alves, Nuno
    Amado, Duarte
    Ferreira, Joana
    Cunha, João Paulo
    Macular Ganglion Cell Layer and Peripapillary Retinal Nerve Fibre Layer Thickness in Patients with Unilateral Posterior Cerebral Artery Ischaemic Lesion: An Optical Coherence Tomography Study2016In: Neuro-ophthalmology (Aeolus Press. 1980), ISSN 0165-8107, E-ISSN 1744-506X, Vol. 40, no 1, p. 8-15Article in journal (Refereed)
    Abstract [en]

    The purpose of this study is to evaluate the macular ganglion cell layer (GCL) and peripapillary retinal nerve fibre layer (RNFL) thickness in patients with unilateral posterior cerebral artery (PCA) ischaemic lesions using spectral-domain optical coherence tomography (SD-OCT). A prospective, case-control study of patients with unilateral PCA lesion was conducted in the neuro-ophthalmology clinic of Centro Hospitalar Lisboa Central. Macular and peripapillary SD-OCT scans were performed in both eyes of each patient. Twelve patients with PCA lesions (stroke group) and 12 healthy normal controls were included in this study. Peripapillary RNFL comparison between both eyes of the same subject in the stroke group found a thinning in the superior-temporal (p = 0.008) and inferior-temporal (p = 0.023) sectors of the ipsilateral eye and nasal sector (p = 0.003) of the contralateral eye. Macular GCL thickness comparison showed a reduction temporally in the ipsilateral eye (p = 0.004) and nasally in the contralateral eye (p = 0.002). Peripapillary RNFL thickness was significantly reduced in both eyes of patients with PCA compared with controls, affecting all sectors in the contralateral eye and predominantly temporal sectors in the ipsilateral eye. A statistically significant decrease in macular GCL thickness was found in both hemiretinas of both eyes of stroke patients when compared with controls (p < 0.05). This study shows that TRD may play a role in the physiopathology of lesions of the posterior visual pathway.

  • 6.
    Artzén, Ditte
    et al.
    S:t Erik Eye Hospital, Stockholm.
    Lundström, Mats
    EyeNet Sweden, Blekinge Hospital, Karlskrona.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Stenevi, Ulf
    Sahlgrenska University Hospital, Mölndal, .
    Lydahl, Eva
    Lake Mälare Hospital, Eskilstuna.
    Montan, Per
    St. Erik Eye Hospital, Stockholm.
    Capsule complication during cataract surgery: Case-control study of preoperative and intraoperative risk factors: Swedish Capsule Rupture Study Group report 2.2009In: Journal of cataract and refractive surgery, ISSN 0886-3350, E-ISSN 1873-4502, ISSN ISSN 0886-3350, Vol. 35, no 10, p. 1688-1693Article in journal (Refereed)
    Abstract [en]

    Abstract

    PURPOSE: To identify preoperative and intraoperative factors associated with a capsule complication; that is, a capsule tear or a zonular dehiscence during cataract surgery. SETTING: Ten ophthalmic surgery departments in Sweden. METHODS: A retrospective review of files of patients with a capsule complication and control patients with no complication operated on in 2003 was performed. RESULTS: The review comprised 324 patients with a capsule complication and 331 control patients. In the logistic regression analyses, preoperative conditions associated with a capsule complication were previous trauma, white and brunescent/hard cataract, and phacodonesis. The intraoperative factors of loose zonules, the use of trypan blue, and miosis were all statistically significantly overrepresented in the capsule complication group. The same was true for eyes operated on by surgeons with the least experience. CONCLUSIONS: By preoperatively identifying cataract cases with the identified risk factors and allocating them to surgeons with the longest experience, the number of capsule complications could be kept low. Operating early in the course of the disease to prevent the cataract from becoming a poor surgical risk and improving training of junior surgeons should further reduce the frequency of capsule complications.

  • 7.
    Aström, Siv
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Incidence and prevalence of pseudoexfoliation and open-angle glaucoma in northern Sweden: I. Baseline report.2007In: Acta Ophthalmologica Scandinavica, ISSN 1395-3907, E-ISSN 1600-0420, Vol. 85, no 8, p. 828-831Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To evaluate the prevalence of pseudoexfoliation (PEX) syndrome and open-angle glaucoma (OAG) among 66-year-old people in the municipality of Skellefteå in northern Sweden.

    METHODS: A population-based study comprising 339 individuals, representing 40% of the age group and 87% of those randomly selected. The examination included tonometry, dilated slit-lamp biomicroscopy, optic disc evaluation and a visual field analysis if glaucoma was suspected.

    RESULTS: The overall prevalence of PEX syndrome was 23%[95% confidence interval (CI): 20-26%], 29% (CI: 24-34%) in women and 15% (CI: 10-19%) in men (P < 0.01). The intraocular pressure (IOP) in PEX eyes was higher (17.3 mmHg, SD 4.5 mmHg) than in eyes without PEX [15.7 mmHg, SD 3.7 mmHg; P < 0.001]. IOP exceeded 22 mmHg in 17% (CI: 11-23%) of the PEX eyes and in 3.0% (CI: 1.9-4.1%) of the non-PEX eyes. Seven individuals (2.1%) had OAG. Six were associated with PEX, i.e. 7.7% of the PEX individuals.

    CONCLUSION: PEX syndrome is common in northern Sweden, affecting every fourth individual reaching the age of 66 years. The prevalence in women is twice that in men. Elevated IOP is roughly six times more frequent in eyes with PEX than in eyes without PEX syndrome. The prevalence of OAG is 2.1%.

  • 8. Backstrom, Gunnie
    et al.
    Lundberg, Björn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Intracameral acetylcholine effectively contracts pupils after dilatation with intracameral mydriatics2013In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 91, no 2, p. 123-126Article in journal (Refereed)
    Abstract [en]

    Purpose: To determine whether intracameral acetylcholine can contract pupils dilated with intracameral mydriatics in phacoemulsification cataract surgery. Methods: A total of 60 patients were included in this prospective randomized masked study performed at ornskoldsviks Hospital Eye Clinic. The patients were randomized and were given either topical placebo and an intracameral mydriatic solution (ICM) (cyclopentolate 0.1%, phenylephrine 1.5% and xylocaine 1%) (n=30) or topical mydriatics (TM) (cyclopentolate 0.85% and phenylephrine 1.5%) and xylocaine 1% intracamerally (n=30) at the start of surgery. After intraocular lens (IOL) implantation, 0.15ml 1% acetylcholine was given intracamerally in all cases. The pupil size was registered preoperatively, 45seconds after intracameral injection, after ophthalmic viscosurgical device (OVD) evacuation, 30seconds after acetylcholine injection, 2min after acetylcholine injection and the day after surgery. Results: The pupil contraction and pupil size after acetylcholine injection showed no significant differences at 30seconds (contraction 1.0 +/- 0.4 in ICM group versus 0.9 +/- 0.4 in TM group; p=0.75; size 4.8 +/- 1.1 in the ICM group versus 5.2 +/- 1.1 in the TM group; p=0.24) or at 2min (contraction 1.5 +/- 0.6 in the ICM group versus 1.4 +/- 0.6 in the TM group; p=0.63; size 4.3 +/- 0.9 in the ICM group versus 4.7 +/- 1.0 in the TM group; p=0.13). No difference in baseline pupil size after ophthalmic viscosurgical device (OVD) evacuation was seen between the two groups (5.8 +/- 0.9 in the ICM group versus 6.1 +/- 1.2 in the TM group; p=0.28). Conclusion: We here show that intracameral acetylcholine contracts pupils as effectively after dilatation with intracameral mydriatics as after dilatation with topical mydriatics. Cataract surgeons can feel comfortable and safe when using intracameral mydriatics, even if pupil contraction with acetylcholine should be required.

  • 9.
    Beckman Rehnman, Jeannette
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    New methods to evaluate the effect of conventional and modified crosslinking treatment for keratoconus2015Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Today corneal crosslinking with ultraviolet-A photoactivation of riboflavin is an established method to halt the progression of keratoconus. In some cases, when the refractive errors are large and the visual acuity is low, conventional corneal crosslinking may not be sufficient. In these cases it would be desirable with a treatment that both halts the progression and also reduces the refractive errors and improves the quality of vision.

    Aims:  The aims of this thesis were to determine whether mechanical compression of the cornea during corneal crosslinking for keratoconus using a sutured rigid contact lens could improve the optical and visual outcomes of the treatment, and also to find methods to evaluate the effect of different corneal crosslinking treatment regimens.

    Methods: In a prospective, open, randomized case-control study, 60 eyes of 43 patients with progressive keratoconus, aged 18-28 years, planned for routine corneal crosslinking, and a corresponding age- and sex-matched control group was included. The patients were randomized to conventional corneal crosslinking (CXL; n=30) or corneal crosslinking with mechanical compression of the cornea during the treatment (CRXL; n=30).

    Biomicroscopy, autorefractometry, best spectacle corrected visual acuity, axial length measurement, Pentacam® HR Scheimpflug photography, pachymetry, intraocular pressure measurements and corneal biomechanical assessments were performed before treatment (baseline) and at 1 month and 6 months after the treatment.

    One of the articles evaluated and compared the optical and visual outcomes between CXL and CRXL, while the other three articles focused on methods to evaluate treatment effects. In Paper I, the corneal light scattering was manually quantified from Scheimpflug images throughout the corneal thickness at 8 measurements points, 0.0 to 3.0 mm from the corneal centre, in patients treated with CXL. In Paper IV the corneal densitometry (light scattering) was measured with the Pentacam® HR software, in 4 circular zones around the corneal apex and at 3 different depths of the corneal stroma, in both CXL and CRXL treated corneas. Paper III quantified the biomechanical effects of CXL in vivo.

    Results: Corneal light scattering after CXL showed distinctive spatial and temporal profiles and Applanation Resonance Tonometry (ART) -technology demonstrated an increased corneal hysteresis 1 and 6 months after CXL. When comparing the refractive and structural results after CXL and CRXL, CRXL failed to flatten the cornea, and the treatment did not show any benefits to conventional CXL treatment, some variables even indicated an inferior effect. Accordingly, the increase in corneal densitometry was also less pronounced after CRXL.

    Conclusions: Analysis of corneal light scattering/densitometry shows tissue changes at the expected treatment location, and may be a relevant variable in evaluating the crosslinking effect. ART -technology is an in vivo method with the potential to assess the increased corneal hysteresis after CXL treatment. By refining the method, ARTmay become a useful tool in the future. Unfortunately, CRXL does not improve the optical and visual outcomes after corneal crosslinking. Possibly, stronger crosslinking would be necessary to stabilize the cornea in a flattened position.

  • 10.
    Beckman Rehnman, Jeannette
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Hallberg, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Increased corneal hysteresis after corneal collagen crosslinking: a study based on applanation resonance technology2014In: JAMA ophthalmology, ISSN 2168-6165, E-ISSN 2168-6173, Vol. 132, no 12, p. 1426-1432Article in journal (Refereed)
    Abstract [en]

    Importance: A reliable tool for quantification of the biomechanical status of the cornea in conjunction with corneal collagen crosslinking (CXL) treatment is needed.

    Objective: To quantify the biomechanical effects of CXL in vivo.

    Design, Setting, and Participants: A prospective, open, case-control study was conducted at the Department of Ophthalmology, Umeå University, Umeå, Sweden. Participants included 28 patients (29 eyes) aged 18 to 28 years with progressive keratoconus and corresponding age- and sex-matched healthy individuals serving as controls. All participants were monitored during a 6-month period between October 13, 2009, and November 5, 2012.

    Main Outcomes and Measures: Corneal hysteresis after CXL for keratoconus.

    Results: A difference in corneal hysteresis between the control group and the patients with keratoconus was found at baseline, both with an applanation resonance tonometer (ART) and an ocular response analyzer (ORA), at mean (SD) values of -1.09 (1.92) mm Hg (99% CI, -2.26 to 0.07; P = .01) and -2.67 (2.55) mm Hg (99% CI, -4.05 to -1.32; P < .001), respectively. Increased corneal hysteresis was demonstrated with an ART 1 and 6 months after CXL, at 1.2 (2.4) mm Hg (99% CI,-0.1 to 2.5; P = .02) and 1.1 (2.7) mm Hg (99% CI, -0.3 to 2.6; P = .04), respectively, but not with ORA. A decrease in corneal thickness was seen 1 and 6 months after treatment (-24 [26] µm, P < .001; and -11 [21] µm, P = .01, respectively), and a corneal flattening of -0.6 (0.7) diopters was seen at 6 months (P < .001). No significant change in intraocular pressure was identified in patients with keratoconus with any method, except for an increase at 1 month with Goldmann applanation tonometry (P = .005).

    Conclusions and Relevance: To our knowledge ART is the first in vivo method able to assess the increased corneal hysteresis after CXL treatment. Given the large-scale use of CXL in modern keratoconus treatment, a tool with this capacity has a great potential value. Refinement of the ART method of measuring and quantifying corneal biomechanical properties will be a subject of further studies.

  • 11.
    Beckman Rehnman, Jeannette
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Hallberg, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Initial results from mechanical compression of the cornea during crosslinking for keratoconus2014In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 92, no 7, p. 644-649Article in journal (Refereed)
    Abstract [en]

    Purpose: To compare refractive changes after corneal crosslinking with and without mechanical compression of the cornea.

    Methods: In a prospective, open, randomized case-control study conducted at the Department of Ophthalmology, Umeå University Hospital, Sweden, sixty eyes of 43 patients with progressive keratoconus aged 18-28 years planned for corneal crosslinking and corresponding age- and sex-matched control subjects were included. The patients were randomized to conventional corneal crosslinking (CXL; n = 30) or corneal crosslinking with mechanical compression using a flat rigid contact lens sutured to the cornea during treatment (CRXL; n = 30). Subjective refraction and ETDRS best spectacle-corrected visual acuity (BSCVA), axial length measurement, keratometry and pachymetry were performed before and 1 and 6 months after treatment.

    Results: The keratoconus patients had poorer BSCVA, higher refractive astigmatism and higher keratometry readings than the control subjects at baseline (p < 0.01). In the CXL group, BSCVA increased from 0.19 ± 0.26 to 0.14 ± 0.18 logMar (p = 0.03), and the spherical equivalent improved from -1.9 ± 2.8 D to -1.4 ± 2.4 D (p = 0.03). Maximum keratometry readings decreased after CXL from 53.1 ± 4.9 D to 52.6 ± 5.2 D (p = 0.02), and the axial length decreased in the CXL group, likely due to post-treatment corneal thinning (p = 0.03). In the CRXL group, all the above variables were unaltered (p > 0.05).

    Conclusion: At 6 months, the refractive results from CRXL did not surpass those of conventional CXL treatment. Rather, some variables indicated a slightly inferior effect. Possibly, stronger crosslinking would be necessary to stabilize the cornea in the flattened configuration achieved by the rigid contact lens.

  • 12.
    Beckman Rehnman, Jeannette
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Janbaz, Chris C.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Spatial distribution of corneal light scattering after corneal collagen crosslinking2011In: Journal of cataract and refractive surgery, ISSN 0886-3350, E-ISSN 1873-4502, Vol. 37, no 11, p. 1939-1944Article in journal (Refereed)
    Abstract [en]

    Purpose: To assess the spatial distribution and time course of increased corneal light scattering after corneal collagen crosslinking (CXL) with riboflavin and ultraviolet-A irradiation.

    Setting: Umeå University Hospital Eye Clinic, Umeå, Sweden.

    Design: Case series.

    Methods: Eyes with keratoconus were examined with Scheimpflug photography before and 1 and 6 months after CXL. Corneal light scattering was quantified throughout the corneal thickness at 8 measurement points 0.0 to 3.0 mm from the central cornea.

    Results: The study comprised 11 eyes of 11 patients. Central corneal light scattering increased significantly 1 month after CXL (P<.001). At 6 months, it decreased (P=.002); however, it was still higher than pretreatment values (P<.001). Light scattering at 1 month was more pronounced in the superficialstroma, gradually diminishing to zero at 240 μm depth. It was greater at the corneal center than 1.0 to 3.0 mm from the center. At 6 months, a second peak of light scattering occurred between 240 μm and 340 μm depth. No increased light scattering deeper than 340 μm was seen at either time point.

    Conclusions: Corneal light scattering after CXL showed distinctive spatial and temporal profiles. Analysis of corneal light scattering may give an impression of tissue changes, the depth of the CXL treatment effect, and the corneal response to the treatment. Scheimpflug photography appears to be useful for this purpose.

  • 13.
    Beckman Rehnman, Jeannette
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Lindén, Christina
    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, Department of Applied Physics and Electronics.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Treatment Effect and Corneal Light Scattering With 2 Corneal Cross-linking Protocols: A Randomized Clinical Trial2015In: JAMA ophthalmology, ISSN 2168-6165, E-ISSN 2168-6173, Vol. 133, no 11, p. 1254-1260Article in journal (Refereed)
    Abstract [en]

    Importance: We describe and evaluate a complementary method to indirectly quantify the treatment effect of corneal cross-linking (CXL). Additional methods to indirectly quantify the treatment effect of CXL are needed.

    Objective: To assess the spatial distribution and the time course of the increased corneal densitometry (corneal light backscatter) seen after CXL with riboflavin and UV-A irradiation.

    Design, Setting, and Participants: Open-label randomized clinical trial of 43 patients (60 eyes) who were 18 to 28 years of age and had progressive keratoconus and a plan to be treated with CXL at Umeå University Hospital, Umeå, Sweden. The patients were randomized to receive conventional CXL (n = 30) using the Dresden protocol or CXL with mechanical compression of the cornea using a flat rigid contact lens sutured to the cornea during the treatment (CRXL) (n = 30). All participants were followed up during a 6-month period from October 13, 2009, through May 31, 2012.

    Interventions: Corneal cross-linking according to the Dresden protocol or CRXL.

    Main Outcomes and Measures: Change in corneal densitometry after CXL and CRXL for keratoconus.

    Results: Of the original 60 eyes included, 4 had incomplete data. A densitometry increase was seen after both treatments that was deeper and more pronounced in the CXL group (difference between the groups at 1 month in the center layer, zone 0-2 mm, 5.02 grayscale units [GSU], 95% CI, 2.92-7.12 GSU; P < .001). This increase diminished with time but was still noticeable at 6 months (difference between the groups at 6 months in the center layer, zone 0-2 mm, 3.47 GSU; 95% CI, 1.72-5.23 GSU; P < .001) and was proportional to the reduction in corneal steepness (R = -0.45 and -0.56 for CXL and CRXL, respectively).

    Conclusions and Relevance: The degree of corneal light backscatter relates to the reduction in corneal steepness after cross-linking and may become a relevant complement to other methods in evaluating the cross-linking effect, for example, when comparing different treatment regimens.

    Trial Registration: clinicaltrials.gov Identifier: NCT02425150.

  • 14. Behndig, A
    et al.
    Karlsson, K
    Johansson, B O
    Brännström, T
    Marklund, S L
    Superoxide dismutase isoenzymes in the normal and diseased human cornea.2001In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 42, no 10, p. 2293-6Article in journal (Refereed)
    Abstract [en]

    PURPOSE: The human cornea, a tissue much exposed to oxidative stress, is rich in extracellular superoxide dismutase (SOD). In this study, the contents and distributions of the SOD isoenzymes in the normal human cornea were compared with those in corneas affected by keratoconus and bullous keratopathy.

    METHODS: The central and peripheral parts of normal human corneas were analyzed separately. Central corneal buttons were obtained from patients with keratoconus and bullous keratopathy who were undergoing primary keratoplasty or retransplantation. SOD enzymatic activities were determined by a direct spectrophotometric method, and extracellular SOD and the cytosolic Cu- and Zn-containing SOD (CuZn-SOD) proteins were determined with ELISA and studied with immunohistochemistry.

    RESULTS: The total SOD content, and particularly the extracellular SOD content, was lower in the central than in the peripheral normal cornea. CuZn-SOD and extracellular SOD were demonstrated in all three corneal layers. CuZn-SOD was found in cells, whereas extracellular SOD appeared to be localized on cell surfaces, in basal membranes, and in the stroma. In keratoconus, corneal levels of extracellular SOD were half those in the control corneas, whereas CuZn-SOD and the mitochondrial Mn-containing SOD levels were normal. In bullous keratopathy, apart from edematous dilution, SOD isoenzyme levels were essentially normal. In a remarkable finding, the same pattern in SOD isoenzyme levels as in the original disease was also found at retransplantation.

    CONCLUSIONS: Extracellular SOD and CuZn-SOD show markedly different distribution patterns within the human cornea. Extracellular SOD activity in the central cornea is halved in keratoconus, compared with that in normal control corneas. The finding of a similar reduction at retransplantation in keratoconus suggests reduced corneal extracellular SOD synthesis in cells of the host as a cause of the low enzyme levels.

  • 15.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    A case of unilateral acid burn.2003In: Acta Ophthalmologica Scandinavica, ISSN 1395-3907, E-ISSN 1600-0420, Vol. 81, no 5, p. 526-529Article in journal (Refereed)
  • 16.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Corneal Collagen Crosslinking for Ectasia after Refractive Surgery2017In: Ophthalmology (Rochester, Minn.), ISSN 0161-6420, E-ISSN 1549-4713, Vol. 124, no 10, p. 1440-1441Article in journal (Other academic)
  • 17.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Effects on pupil size and accommodation from topical lidocaine hydrochloride and tetracaine hydrochloride.2007In: Journal of Ocular Pharmacology and Therapeutics, ISSN 1080-7683, E-ISSN 1557-7732, Vol. 23, no 6, p. 591-8Article in journal (Refereed)
    Abstract [en]

    PURPOSE: The aim of this study was to quantify the mydriatic and cycloplegic effects from topically applied lidocaine hydrochloride 4% and tetracaine hydrochloride 1% in healthy volunteers. METHODS: Twenty-six (26) healthy volunteers age 23 +/- 2.5 years were included in this double-masked, randomized, intraindividually comparing study. All participants were given a drop of lidocaine 4% in 1 eye and tetracaine 1% in the contralateral eye three times with a 90-sec interval, which was subject to randomization. Before the eye drops, and 15, 30, 45, 60, 90, and 120 min after the application of the last drop, Scheimpflug photography was performed in each eye, and the near point was determined using a near-point ruler. Before the eye drops and at 60 and 120 min, the visual acuity was determined with the ETDRS chart. The extent and time course of the mydriatic and cycloplegic responses were determined. RESULTS: Significant pupil dilation was seen with both substances; an increase from 3.25 +/- 0.48 to 3.52 +/- 0.76 mm (8.8 +/- 3.9%; P = 0.036) at 30 min with lidocaine, and from 3.19 +/- 0.46 to 3.44 +/- 0.49 mm (8.8 +/- 2.9%; P = 0.008) at 45 min with tetracaine. A subgroup analysis revealed that a mydriatic effect could only be detected in eyes with pale irides (P < 0.01). In pigmented irides, a slight miotic effect was noted. A decrease in accommodation was also seen: from 9.8 +/- 1.6 to 9.1 +/- 1.7 D (6.3 +/- 2.9%) at 15 min with lidocaine, and from 9.7 +/- 1.4 to 8.8 +/- 1.5 D (7.8 +/- 3.7%) at 30 min with tetracaine. Again, the effect was more pronounced in pale irides (P < 0.05). Both substances induced a small increase in corneal thickness (P < 0.01). A substantial epithelial opacification was noted with tetracaine, but not with lidocaine. CONCLUSIONS: Lidocaine 4% and tetracaine 1% exhibit significant mydriatic effects upon topical administration in eyes with pale irides. The mydriatic effect is more rapid and prolonged with lidocaine than with tetracaine.

  • 18.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Immediate sequential cataract surgery: the pros and cons of a controversial approach.2009In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 87, no 1, p. 2-3Article in journal (Refereed)
  • 19.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Phacoemulsification in spherophakia with corneal touch2002In: Journal of cataract and refractive surgery, ISSN 0886-3350, E-ISSN 1873-4502, Vol. 28, no 1, p. 189-191Article in journal (Refereed)
    Abstract [en]

    A phacoemulsification procedure with implantation of a foldable acrylic intraocular lens in a 31-year-old man with spherophakia is described. The procedure was necessitated by anterior dislocation of the spherophakic lens, with corneal endothelial contact and development of central corneal edema. With a careful approach, the procedure was uneventful and the outcome successful. Modern small-incision cataract surgery techniques are of great benefit in this type of complicated case.

  • 20.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Results with a modified method for scleral suturing of intraocular lenses.2002In: Acta Ophthalmologica Scandinavica, ISSN 1395-3907, E-ISSN 1600-0420, Vol. 80, no 1, p. 16-18Article in journal (Refereed)
    Abstract [en]

    PURPOSE / METHODS: The long-term results obtained by a modified method of scleral suturing of posterior chamber lenses (PCLs) (Behndig & Otto 1997) were retrospectively registered and evaluated. Forty-four patients with insufficient capsular support for ordinary PCL implantation were included. Mean follow-up time was 13.1 +/- 6.4 months and registered parameters included visual acuity, deviation from planned refractive outcome, induced astigmatism, and complications. RESULTS / CONCLUSIONS: The results were comparable to those reported earlier for this type of surgery. It has previously been stated that scleral suturing of posterior chamber lenses is a safe procedure with good long-term results. This modified method produces comparable results while being more surgically simple and reproducible.

  • 21.
    Behndig, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Cochener, Beatrice
    Luis Gueell, Jose
    Kodjikian, Laurent
    Mencucci, Rita
    Nuijts, Rudy M. M. A.
    Pleyer, Uwe
    Rosen, Paul
    Szaflik, Jacek P.
    Tassignon, Marie-Jose
    Endophthalmitis prophylaxis in cataract surgery: Overview of current practice patterns in 9 European countries2013In: Journal of cataract and refractive surgery, ISSN 0886-3350, E-ISSN 1873-4502, Vol. 39, no 9, p. 1421-1431Article, review/survey (Refereed)
    Abstract [en]

    Data on practice patterns for prophylaxis against infectious postoperative endophthalmitis (IPOE) during cataract surgery in 9 European countries were searched in national registers and reviews of published surveys. Summary reports assessed each nation's IPOE rates, nonantibiotic prophylactic routines, topical and intracameral antibiotic use, and coherence to the European Society of Cataract & Refractive Surgeons (ESCRS) 2007 guidelines. Although the reliability and completeness of available data vary between countries, the results show that IPOE rates differ significantly. Asepsis routines with povidone iodine and postoperative topical antibiotics are generally adopted. Use of preoperative and perioperative topical antibiotics as well as intracameral cefuroxime varies widely between and within countries. Five years after publication of the ESCRS guidelines, there is no consensus on intracameral cefuroxime use. Major obstacles include legal barriers or persisting controversy about the scientific rationale for systematic intracameral cefuroxime use in some countries and, until recently, lack of a commercially available preparation.

  • 22.
    Behndig, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Eriksson, Anders
    Medocular/Strandvägskliniken, Grevgatan 5, Stockholm, Sweden.
    Evaluation of surgical performance with intracameral mydriatics in phacoemulsification surgery.2004In: Acta Ophthalmologica Scandinavica, ISSN 1395-3907, E-ISSN 1600-0420, Vol. 82, no 2, p. 144-147Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To evaluate surgical performance using intracameral mydriatics (ICM) in phacoemulsification surgery in a series of consecutive cases. METHODS: In a series of 198 consecutive procedures 50-200 microl of cyclopentolate 0.1%, phenylephrine 1.5% and lidocaine 1% was given intracamerally for mydriasis and anaesthesia. The previous 198 cases, dilated with topical mydriatics, were studied for comparison. Several pre- intra- and postoperative parameters were registered, and the subjective surgical performance was graded after each procedure. In 41 consecutive cases, the change in pulse and oxygen saturation induced by the ICM injection was registered. RESULTS: No increase in operation time or complication rates was seen with ICM, compared to when standard topical mydriatics were used. The subjective surgical performance was ranked as equally good for both groups. CONCLUSION: From this clinical evaluation, our impression is that ICM performs well in routine phacoemulsification surgery.

  • 23.
    Behndig, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Aqueous humor lidocaine concentrations in topical and intracameral anesthesia1998In: Journal of cataract and refractive surgery, ISSN 0886-3350, E-ISSN 1873-4502, Vol. 24, no 12, p. 1546-1647Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To assess aqueous humor lidocaine concentrations in 2 common regimens of topical anesthesia and after intracameral injection of the anesthetic agent. SETTING: University hospital eye clinic. METHODS: Twenty patients having routine cataract surgery were randomized into 3 groups: 1 given 3 drops of lidocaine 4% before surgery; 1 given 6 drops; 1 given 3 drops plus an intracameral injection of 0.1 mL lidocaine 1%. Lidocaine concentration was measured in aqueous humor samples taken before surgery. RESULTS: With 3 drops, aqueous lidocaine concentration was 1.4 micrograms/mL +/- 0.5 (SD) and with 6 drops, 4.3 +/- 1.5 micrograms/mL (P = .0015). With an intracameral injection, it was 341.8 +/- 152.6 micrograms/mL. CONCLUSION: Measurable amounts of lidocaine entered the anterior chamber in topical anesthesia, and more entered when more drops were given. It is likely that concentrations in this range could anesthetize the iris, but they are far lower than concentrations after an intracameral injection.

  • 24.
    Behndig, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Lundberg, Björn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Mydriatic response to different concentrations of intracameral phenylephrine in humans2010In: Journal of cataract and refractive surgery, ISSN 0886-3350, E-ISSN 1873-4502, Vol. 36, no 10, p. 1682-1686Article in journal (Refereed)
    Abstract [en]

    Results show that phenylephrine injected intracamerally does not have a linear mydriatic dose-response relationship in humans. At very high concentrations, phenylephrine may bind to and stimulate receptors other than the α(1)-receptor, explaining this phenomenon.

  • 25.
    Behndig, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Lundberg, Björn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Transient corneal edema after phacoemulsification: comparison of 3 viscoelastic regimens2002In: Journal of cataract and refractive surgery, ISSN 0886-3350, E-ISSN 1873-4502, Vol. 28, no 9, p. 1551-1556Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To evaluate the effect of different viscoelastic substances on the grade and time course of postoperative corneal edema. SETTING: Department of Clinical Sciences/Ophthalmology, Umeå University Hospital, Umeå, Sweden. METHODS: This study comprised 62 patients with otherwise healthy eyes who had routine phacoemulsification and intraocular lens (IOL) implantation. Patients were divided into 3 groups. Group 1 was given Healon GV (sodium hyaluronate 1.4%) at phacoemulsification and IOL implantation. Group 2 was given Viscoat (sodium hyaluronate 3.0%-chondroitin sulfate 4.0%) at phacoemulsification and Healon GV at IOL implantation. Group 3 was given Viscoat at phacoemulsification and Provisc (sodium hyaluronate 1.0%) at lens implantation. The central corneal thickness was measured with ultrasonic pachymetry before surgery and 5 and 24 hours, 1 week, and 1 month after surgery. RESULTS: The mean increase in corneal thickness was significantly greater in Group 1 than in the other 2 groups 5 and 24 hours and 1 week after surgery. CONCLUSIONS: The transient postoperative increase in central corneal thickness was greater in patients receiving Healon GV during phacoemulsification than in patients receiving Viscoat. The use of Provisc or Healon GV for IOL implantation did not affect the postoperative corneal thickness when Viscoat was used for phacoemulsification. The time course of the edema may be explained by a difference between the 2 agents in endothelial protection from ultrasonic, mechanical, or irrigation trauma.

  • 26.
    Behndig, Anders
    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.
    Determination of the aqueous humor volume by three-dimensional mapping of the anterior chamber.2005In: Ophthalmic Research, ISSN 0030-3747, E-ISSN 1423-0259, Vol. 37, no 1, p. 13-16Article in journal (Refereed)
    Abstract [en]

    In this study involving 12 patients planned for routine cataract surgery, we used the topography of the anterior chamber depth and the corneal diameter obtained from Orbscan II data to calculate the aqueous humor volume. Prior to the surgical procedure, a small amount of fluorescein was injected into the anterior chamber and an aqueous humor sample was taken, from which the aqueous humor volume could be calculated by fluorometry. The volumes obtained from Orbscan II data were validated by the fluorometric measurements and compared to three theoretical formulas for aqueous humor volume calculation. The aqueous humor volume calculations based on the Orbscan II data aligned better to the fluorometric values (R(2) = 0.890) than the values obtained by Heim's formula (R(2) = 0.677), Brubaker's formula (R(2) = 0.671), and Schenker's formula (R(2) = 0.585), or the assumption of a constant aqueous humor volume.

  • 27.
    Behndig, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Montan, Per
    St Eriks ögonsjukhus, Karolinska Institutet, Stockholm.
    Stenevi, Ulf
    Department of Ophthalmology, Sahlgrenska University Hospital, Molndal.
    Kugelberg, Maria
    St Eriks ögonsjukhus, Karolinska Institutet, Stockholm.
    Lundstrom, Mats
    EyeNet Sweden, Blekinge Hospital, Karlskrona, € Sweden.
    One million cataract surgeries: Swedish National Cataract Register 1992-20092011In: Journal of cataract and refractive surgery, ISSN 0886-3350, E-ISSN 1873-4502, Vol. 37, no 8, p. 1539-1545Article in journal (Refereed)
    Abstract [en]

    This review summarizes data collected by the Swedish National Cataract Register, which now contains data pertaining to more than a million cataract surgery procedures, representing 95.6% of the surgeries performed in Sweden during 1992-2009. During this period, the rate of cataract surgery rose from 4.47 to 9.00 per 1000 inhabitants. The mean patient age increased until 1999 but has slowly decreased since then. Preoperative visual acuity has risen steadily. The distribution between the sexes was stable until 2000, after which the proportion of women slowly decreased. Registration of subjective benefit has brought new knowledge regarding indications and expectations. An improved questionnaire, Catquest-9SF has been used since 2008. The outcome register generally shows good results from the surgery. Endophthalmitis has decreased from 0.10% to below 0.040%.

  • 28.
    Behndig, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Montan, Per
    Stenevi, Ulf
    Kugelberg, Maria
    Zetterström, Charlotta
    Lundström, Mats
    Aiming for emmetropia after cataract surgery: Swedish National Cataract Register study2012In: Journal of cataract and refractive surgery, ISSN 0886-3350, E-ISSN 1873-4502, Vol. 38, no 7, p. 1181-1186Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To assess and analyze refractive outcome after cataract surgery in Sweden from 2008 though 2010. SETTING: Swedish cataract surgery units participating in outcome registration of National Cataract Register. DESIGN: Cohort study. METHODS: Planned and actual postoperative refractions were analyzed for cataract procedures and preoperative and postoperative corneal astigmatism for procedures performed in 2008 though 2010. Induced astigmatism was calculated with Naeser and Behrens polar coordinates. RESULTS: Postoperative refraction was analyzed for 17 056 procedures and corneal astigmatism for 7448 procedures. Emmetropia was targeted in 78.1% of eyes and achieved in 52.7%; 43.0% had less than 1.00 diopter (D) of astigmatism. "Reading myopia" of -3.5 to -1.6 D was targeted in 7.0% of eyes and achieved in 7.8%. Planned hyperopia greater than 1.0 D or myopia greater than -3.5 D was rare. The mean absolute biometry prediction error was 0.402 D +/- 0.338 (SD) in all eyes; however, astigmatic eyes and eyes planned for myopia or hyperopia had higher biometry prediction errors. Younger patients were more often astigmatic and planned for a more myopic outcome. Preoperatively, one third of eyes had more than 1.0 D of corneal astigmatism; postoperatively this figure was largely unaltered. The mean induced astigmatism was 0.525 +/- 0.804 D in all eyes. CONCLUSIONS: Emmetropia (spherical equivalent -0.5 to + 0.5 D and <1.0 D astigmatism) is the goal in most cataract cases but was reached in only 55% of eyes planned for emmetropia. Factors precluding emmetropia included remaining corneal astigmatism and biometry prediction errors in astigmatic and ametropic eyes.

  • 29.
    Björkblom, Benny
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Eidet, Jon R.
    Utheim, Tor P.
    Ulltveit-Moe, Harald F.
    Raeder, Sten
    Xenobiotic- and Serum-Free Culture of Oral Mucosal Epithelial Cells on Contact Lenses2016In: Current Eye Research, ISSN 0271-3683, E-ISSN 1460-2202, Vol. 41, no 1, p. 20-27Article in journal (Refereed)
    Abstract [en]

    Purpose/aim: Cultured autologous oral mucosal epithelial cells (OMECs) have proven useful in the treatment of ocular surface disorders. This study is the first to investigate the potential of expanding OMEC in a xenobiotic- and serum-free medium using therapeutic contact lenses (CLs) as a substrate and carrier.

    Materials and methods: Porcine OMEC were seeded on laminin-coated lotrafilcon A therapeutic CLs with the density of 8x10(4)cells/lens and cultured in a defined serum and xenobiotic-free medium. Confocal immunofluorescence microscopy was used to analyze the following: (1) cellular morphology by using rhodamine-phalloidin staining of F-actin, (2) phenotype by applying antibodies against the progenitor cell marker p63 and the putative stem cell marker ABCG2 and (3) cell viability by using propidium iodide and Hoechst 33342 dual staining.

    Results: Porcine OMEC attached well to the CLs, and cell-to-cell contacts were evident. After three days in culture, the OMEC displayed a confluent monolayer with uniform cobblestone morphology, whereas stratified cultures with 2-3 layers were formed after six days. No significant difference in expression of p63 was observed after three-day culture (79.414.8%) compared with six-day culture (60.3 +/- 18.9%). ABCG2 expression in the basal cell layer was 6.3 +/- 1.0% and 4.8 +/- 1.8% after three- and six-day culture, respectively. The basal layer viability of cultured OMECs was 99.3 +/- 0.2% and 82.8 +/- 1.1% after three and six days culture, respectively.

    Conclusions: The use of therapeutic CLs has potential as a substrate and carrier for OMEC cultured in a xenobiotic- and serum-free culture system.

  • 30.
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Cataract surgery in ancient Egypt2014In: Journal of cataract and refractive surgery, ISSN 0886-3350, E-ISSN 1873-4502, Vol. 40, no 3, p. 485-489Article, review/survey (Refereed)
    Abstract [en]

    Ophthalmology was one of the most important specialties in Egyptian medicine, and more specialists are known in this field than in any other. This specialization seems, however, to have been of a purely noninvasive nature. Even though it has been claimed that cataract surgery was performed in pharaonic Egypt, careful analysis of the sources does not support the claim. No example of cataract surgery or of any other invasive ophthalmologic procedure can be found in the original sources.

  • 31.
    Borbely, Gabor
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Löfgren, Filip
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Sloniecka, Marta
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Backman, Ludvig J.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Danielson, Patrik
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    The role of neurokinin A in corneal wound repair2015In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 56, no 7, article id Meeting Abstract: 725Article in journal (Other academic)
  • 32.
    Burstedt, Marie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Bothnia dystrophy, a clinical, genetical and electrophysiological study2003Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    A high frequency of retinitis pigmentosa (RP) is found in Northern Sweden. In an inventory of autosomal recessive RP patients in Västerbotten County, a great number of cases with a unique phenotype was noticed, denoted Bothnia Dystrophy (BD). The aim of the study was to describe the phenotype, to determine the chromosomal location, and to identify the gene.

    Patients typically show night blindness from early childhood. Symptoms of defect macular function with a decrease of visual acuity can appear in early adulthood. The retinal fundus shows irregular white spots in a central, and parafoveal pattern along the arcades. Centrally areolar maculopathy develops and round circular atrophies are observed in the periphery.

    The disease was shown to be associated with a missense mutation in the RLBP1 gene resulting in an amino acid substitution (R234W) in the cellular retinaldehyde-binding protein (CRALBP). The R234W mutation was found in a homozygous state in 61 patients affected with BD. Ten patients were heterozygous for the R234W mutation, and presented a similar phenotype. No additional mutations in the coding sequence or exon-intron junctions were found. CRALBP is localised in retinal pigment epithelium (RPE), and Müller cells of the retina. In the RPE, CRALBP functions as a carrier protein for endogenous retinoids.

    Dark adaptometry and electrophysiologic testing showed an initial loss of rod function followed by a progressive reduction of the cone responses in older ages. A compromised rod function, dysfunction of the Müller cells, and indications of a disturbed function of the inner retina were found. With prolonged dark adaptation, a gradual increase in retinal sensitivity to light and an improvement of the ERG components occurred. The findings indicate a prolonged synthesis of photopigments, retardation of the visual process in the retinal pigment epithelium and a loss of retinal cells probably starting at a relative early age in BD.

    To evaluate the subjective visual function in BD patients, a battery of objective tests of visual function and composite score of the 25-item NEI-Visual Function Questionnaire (VFQ-25) were analyzed. We found that weighted distance logMAR visual acuity (WVA), had the strongest association with subjective visual function, and that there was a considerable loss of subjective and objective visual function with increasing age in BD patients. The prevalence of BD is as high as 1:3600 in Västerbotten County.

    The possibility that recycling of retinoids localized in the RPE might be impaired in BD might give future therapeutic possibilities. Due to the large and clinically well-characterized set of patients with this disease, they constitute a suitable study group.

  • 33.
    Burstedt, Marie
    et al.
    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.
    Central Retinal Findings in Bothnia Dystrophy Caused by RLBP1 Sequence Variation2010In: Archives of ophthalmology (1960), ISSN 0003-9950, Vol. 128, no 8, p. 989-995Article in journal (Refereed)
    Abstract [en]

    Objective: To describe the central retinal findings early in the course of Bothnia dystrophy caused by the homozygous missense R234W sequence variation in the RLBP1 gene. Methods: In 8 young patients with Bothnia dystrophy (aged 9-34 years), high- and low-contrast distance visual acuity and visual fields were measured with Humphrey central (24-2) threshold testing and Goldmann perimetry. Central retinal thickness was measured with optical coherence tomography. Cross-sectional images were analyzed and a linear scanning protocol was applied to examine retinitis punctata albescence in the posterior pole. Results: Affected visual acuity (4 of 8 cases) and poor low-contrast visual acuity (8 of 8 cases) were found. Significant foveal depression and visual field loss were evident with Humphrey threshold testing at all ages, and paracentral and central scotomata in the second decade of life advanced in adulthood as verified with Goldmann perimetry. Optical coherence tomography showed generalized retinal thinning in the central foveal, foveal (innermost ring diameter [empty set], 1 mm), and inner ring (empty set, 3 mm) areas in all ages, and early retinal thinning was found in the inferior areas of the outer macula (empty set, 6 mm). Foveal and extrafoveal thinning of the retinal layers and outer nuclear layer were found. Homogeneous retinitis punctata albescence changes were visualized in and/or adjacent to the retinal pigment epithelium choriocapillaris complex with high reflectance. Conclusions: In the RLBP1 Bothnia dystrophy phenotype, a loss of function and thinning of the central macula are found, indicating early damage of the cone photoreceptors in this disease of the visual cycle. Retinitis punctata albescence spots in the posterior pole are situated close to or in the retinal pigment epithelium-choriocapillaris complex.

  • 34.
    Burstedt, Marie S I
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Ristoff, Ellinor
    Larsson, Agne
    Wachtmeister, Lillemor
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Rod-cone dystrophy with maculopathy in genetic glutathione synthetase deficiency: a morphologic and electrophysiologic study.2009In: Ophthalmology, ISSN 1549-4713, Vol. 116, no 2, p. 324-331Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To describe the retinal findings in 2 young adults with glutathione synthetase (GS) deficiency, an autosomal-recessive inborn error of glutathione (GSH) metabolism. DESIGN: Report of 2 cases. PARTICIPANTS: Binocular study in 2 affected siblings. METHODS: Two sisters with severe GS deficiency underwent a first ophthalmologic examination including full-field electroretinogram (ERGs). The single flash and flicker ERGs and the oscillatory potentials were measured. The clinical examination was repeated after 1 year with the addition of fluorescein angiography, optical coherence tomography (OCT), and electrooculography (EOG). MAIN OUTCOME MEASURES: Angiograms and the retinal OCTs were analyzed, the morphologic findings compared, and the Arden ratio measured. RESULTS: Myopia decreased in both sisters, and visual acuity remained unchanged. Ophthalmoscopy showed bilateral retinal degenerative changes. Binocular cystic macular edema was present in the fovea and perifoveal areas. Cystic changes were located in the inner nuclear layer and outer plexiform layer. The ERGs showed low or no recordable rod-isolated b-waves, mixed rod-cone a- and b-waves, and cone responses. The oscillatory potentials were subnormal or nonrecordable. The EOG values were subnormal except in 1 eye of the older sister that had a normal Arden ratio. CONCLUSIONS: Severe GS deficiency is associated with progressive retinal dystrophy of the rod-cone type, affecting the central retina with advanced macular edema in adulthood. The retinal degenerative changes in GS deficiency may be the result of the increased oxidative stress accumulated generally in the retina and also apparent in the macular area, and an insufficient level of the free radical scavenger GSH. The patients with GS deficiency may represent a model of the retinal response to oxidative stress in humans. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this paper.

  • 35.
    Burstedt, Marie S I
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Sandgren, Ola
    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. Medicinsk och klinisk genetik.
    Wachtmeister, Lillemor
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Effects of prolonged dark adaptation in patients with retinitis pigmentosa of Bothnia type: an electrophysiological study.2008In: Doc Ophthalmol, ISSN 0012-4486, Vol. 116, no 3, p. 193-205Article in journal (Other academic)
    Abstract [en]

    Bothnia dystrophy (BD) is a variant of recessive retinitis punctata albescens (RPA), caused by the missense mutation R233W in cellular retinaldehyde-binding protein (CRALBP), which is localized in the retinal pigment epithelium (RPE) and Müller cells of the retina. The purpose of this study was, by examining the electrophysiological responses of the retina, to evaluate the capacity of recovery of the whole retinal area and different cell types induced by extremely prolonged dark adaptation (DA) in BD disease and to gain further understanding of the pathogenesis of BD. Six young patients underwent bilateral full-field ERGs after 24 h of DA in one eye and standard DA in the fellow eye. The results were also compared with the effect of prolonged DA (10 h), previously studied in the same patients. After extremely prolonged DA (24 h) the rod b-wave and the mixed rod-cone a-wave responses reached normal though delayed amplitudes. An increase, up to normal level, in the oscillatory response was found. There was no obvious recovery of the cone response. We conclude that in young BD patients during extremely prolonged DA there is a significant additional capacity of recovery of rod function and also significant gain of activity in the inner retinal layer. A continuous but slow regeneration of rod photopigment seems to occur at least up to 24 h. The visual process in the RPE is retarded and CRALBP acts in this process; also, the Müller cells of the retina seem to be involved. The findings also support an extremely slow synthesis of photopigments and irreversibly disturbed cone function early in BD.

  • 36.
    Burstedt, Marie S I
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Sandgren, Ola
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Golovleva, Irina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Wachtmeister, Lillemor
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Retinal function in Bothnia dystrophy. An electrophysiological study.2003In: Vision Research, ISSN 0042-6989, E-ISSN 1878-5646, Vol. 43, no 24, p. 2559-2571Article in journal (Refereed)
    Abstract [en]

    Using prolonged dark adaptometry, standard dark adaptation (DA) and prolonged DA full-field electroretinograms (ERGs), we analysed the retinal function in patients with Bothnia dystrophy (BD), a variant of recessive retinitis punctata albescens (RPA). A compromised rod and cone function, a likely dysfunction of the Müller cells, and indications of disturbed neuronal function of the inner retina, were found. With prolonged DA, a gradual increase in retinal sensitivity to light and an improvement of the ERG components occurred. The findings indicate a prolonged synthesis of photopigments, retardation of the visual process in the retinal pigment epithelium (RPE), and a loss of retinal cells, probably starting at a relatively early age in BD.

  • 37.
    Burstedt, Marie S
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Mönestam, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Sandgren, Ola
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Associations between specific measures of vision and vision-related quality of life in patients with bothnia dystrophy, a defined type of retinitis pigmentosa.2005In: Retina, ISSN 0275-004X, E-ISSN 1539-2864, Vol. 25, no 3, p. 317-323Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To assess the relationship between objective tests of visual function and vision-related quality of life in patients with Bothnia dystrophy (BD), a retinal dystrophy of retinitis pigmentosa type with progressive maculopathy.

    METHODS: Forty-nine patients were tested. Weighted distance logMAR visual acuity (WVA), weighted logMAR low contrast VA (WCS), and binocular visual field (VF) areas were calculated. Vision-related quality of life (VRQL) was assessed using the 25-item National Eye Institute-Visual Function Questionnaire (NEI-VFQ-25). Correlation statistics were used and adjusted analyses of the relationship between the composite score and the objective visual function tests were performed with multiple linear regression.

    RESULTS: VRQL was significantly correlated with age, WVA, WCS, and binocular VF areas (P < 0.001). Calculation of partial correlation coefficients showed age to be significantly correlated only with VF (V-4-e) area (P < 0.0001). Multiple linear regression analyses revealed age and WVA to be significantly associated with the NEI-VFQ-25 composite score (P < 0.02 and P = 0.001, respectively). WVA alone was the strongest predictor of self-reported experience of total visual function in BD patients (r 2= 0.69).

    CONCLUSIONS: A strong relationship between objective tests of visual function and patient perceived VRQL as assessed by a questionnaire was found. WVA was the strongest predictor and together with age explained almost 70% of the variability of the composite score of the questionnaire.

  • 38.
    Burstedt, Marie Si
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Mönestam, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Self-reported quality of life in patients with retinitis pigmentosa and maculopathy of Bothnia type.2010In: Clinical ophthalmology (Auckland, N.Z.), ISSN 1177-5467, Vol. 4, p. 147-154Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To assess vision-related quality-of-life subscales with objective measurements of visual function in patients affected with retinitis pigmentosa of Bothnia type (BD). METHODS: Forty-nine patients answered the NEI-VFQ-25 questionnaire. High- and low-contrast distance acuity (VA), near VA, and visual fields (VF) were measured. Weighted VA (WVA) and low-contrast (10%) VA (WLCVA), binocular VF areas, and central scotoma were calculated. Adjusted mean subscale scores were calculated and associations analyzed. RESULTS: Subscale scores for general, far, and near vision, social functioning, and color vision were lowest while general health, ocular pain, and mental health were highest in the BD phenotype. The correlations were substantial and similar for WVA, WLCVA, and near vision. The degree of measured VF impairment had few associations with the different adjusted subscale scores. CONCLUSION: The NEI VFQ-25 subscales were well associated with clinical vision measures depending on VA. The progression of VF defects typical for the BD phenotype does not seem to affect the self-perceived quality of life, which might indicate adaptability to this type of progressive VF loss. The BD phenotype has a significant impact on multiple domains of daily life, but there are no signs of accelerating depression related to the increasing visual impairment.

  • 39.
    Byström, Berit
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Laminins and alpha11 integrin in the human eye: importance in development and disease2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The extracellular matrix (ECM) offers a protective shelter for cells and provides signaling paths important for cell to cell communication. ECM consists of basement membranes (BM) and interstitial matrix. BMs provide mechanical support for parenchymal cells, influence cell proliferation, survival, migration and differentiation. They are also important for tissue integrity. Laminins (LM) are the major non-collagenous component of BMs. Cell-ECM interactions, mediated by receptors, are indispensable during embryonic development, wound healing, remodeling and homeostasis of tissues. The integrins are the major cell-adhesion receptors. The expression of alpha11 integrin chain in the cornea is of great interest, as it is part of the alpha11beta1 integrin receptor for collagen type I, the predominant component of the corneal stroma.

    The aims were to thoroughly characterize the ECM in the developing and adult human eye, with particular focus on the cornea, LM and alpha11 integrin chains, and to examine alpha11 integrin chain in an animal model of corneal wound healing and remodeling. Human fetal eyes, 9-20 weeks of gestation (wg), and adult human corneas with different diagnosis were treated for immunohistochemistry with specific antibodies against LM and alpha11 integrin chains. Normal and knockout (ko) mice were treated with laser surgery to create a deep wound in the corneal stroma. The wound healing process was followed at different time points. The cellular source of alpha11 integrin chain was studied in cell cultures.

    In the fetal eyes, the BM of the corneal epithelium, the Descemet’s membrane (DM) and the Bruch’s membrane each had their specific combinations of LM chains and time line of development, whereas the lens capsule and the internal limiting membrane showed constant LM chain patterns.

    The epithelial BMs of normal and diseased adult corneas contained similar LM chains. The normal morphology of the epithelial BM was altered in the different diseases, particularly when scarring was present. In the scarred keratoconus corneas there were excessive LM chains. The majority of keratoconus corneas also expressed extra LM chains in the DM.

    At 10-17 wg alpha11 integrin chain was present in the human corneal stroma, especially in the anterior portion, but it was scarce at 20 wg, in normal adult corneas and in Fuchs’ endothelial dystrophy. In contrast, it was increased in the anterior portion of the stroma in keratoconus corneas with scarring. Alpha11 integrin ko mice had a defective healing with subsequent thinner corneas. Alpha11 integrin expression correlated to the presence of alpha-smooth muscle actin in vivo as well as in vitro.

    The distinct spatial and temporal patterns of distribution for alpha11 integrin and each of the LM chains suggest that they play an important role in human ocular differentiation. The selectively affected LM composition and the novel expression of alpha11 integrin chain in scarred keratoconus corneas as well as the pathologic healing in ko mice, indicate that alpha11 integrin and LM chains also play an important role in the process of corneal healing, remodeling and scarring and might participate in the pathogenesis of corneal disease. This knowledge is of practical importance for future topical therapeutic agents capable of modulating the corneal wound healing processes.

  • 40.
    Byström, Berit
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Carracedo, Sergio
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Gullberg, Donald
    Pedrosa-Domellöf, Fatima
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Alpha11 integrin in the human cornea: importance in development and disease.2009In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 50, no 11, p. 5044-5053Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To examine the distribution of the alpha11 integrin chain in the human cornea during fetal development and in normal and diseased adult human corneas.

    METHODS: Six fetal corneas, 10 to 20 weeks of gestation (wg), and 18 adult corneas including 3 normal, 7 with keratoconus, 5 with pseudophakic bullous keratopathy (PBK), 2 with Fuchs' corneal dystrophy, and 1 with a scar after deep lamellar keratoplasty (DLKP) were processed for immunohistochemistry with specific antibodies against the alpha11 integrin chain; collagen I, IV, and V; and alpha-smooth muscle actin (alpha-SMA). The cellular source of alpha11 integrin chain was further investigated in cell cultures.

    RESULTS: At 10 to 17 wg, the alpha11 integrin chain was predominantly present in the anterior corneal stroma. At 20 wg, in normal adult corneas and in Fuchs' dystrophy corneas there was weak staining in the stroma. The PBK corneas showed variable and weak staining, generally accentuated in the posterior stroma near Descemet's membrane. In contrast, the anterior portion of the stroma in the keratoconus corneas was strongly stained in an irregular streaky pattern. Human corneal fibroblasts/myofibroblasts produced alpha11 integrin chain in culture. Cultures treated with TGF-beta showed higher content of both alpha-SMA and the alpha11 integrin chain.

    CONCLUSIONS: The presence of the alpha11 integrin chain during early corneal development and the enhanced expression in scarred keratoconus corneas indicates that this integrin chain is likely to play an important role in collagen deposition during corneal development and in keratoconus with a scarring component and compromised basement membrane integrity.

  • 41.
    Byström, Berit
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Virtanen, Ismo
    Rousselle, Patricia
    Gullberg, Donald
    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.
    Distribution of laminins in the developing human eye2006In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 47, no 3, p. 777-785Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To examine the distribution of laminin (Ln) chains in basement membranes (BMs) of the human cornea, lens, and retina in fetal development. METHODS: Ten fetal eyes (9-20 weeks of gestation [wg]) were serially sectioned and treated with specific antibodies against the Ln-alpha1, -alpha2, -alpha3, -alpha4, -alpha5, -beta1, -beta2, -beta3, and -gamma1 chains. RESULTS: The BM of the corneal epithelium was reactive for Ln-alpha3, -alpha5, -beta1, and beta3 chains through all ages, whereas the Ln-alpha1 chain was present at 9 to 12 wg and the Ln-alpha4 chain from 10 wg. The Descemet's membrane (DM) was labeled with the Ln-alpha1 and -alpha4 chains at 10 to 17 wg, the Ln-alpha5 chain from 10 wg, the Ln-beta1 chain at 11 to 17 wg, and the Ln-beta3 chain from 17 wg. The Ln-alpha1, alpha5, -beta1, and -beta2 chains were present in the lens capsule and the internal limiting membrane (ILM) through all ages. The Bruch's membrane (BrM) was immunoreactive for the Ln-alpha3, alpha4, -alpha5, -beta1, and -beta2 chains through all ages, whereas the Ln-alpha1 chain was absent from 20 wg onward. The Ln-alpha2 chain was not detected in the eye, but it was present in the extraocular muscles. CONCLUSIONS: BMs play an important role during morphogenesis, in that they influence cell proliferation, migration, and tissue differentiation. Lns are the major noncollagenous component of BMs. The presence of four different alpha chains, three beta chains, and one gamma chain of Ln in the eye reveals a high degree of complexity from the early stages of development and suggests an important role for the different Ln chains in human ocular differentiation.

  • 42.
    Bäckström, Gunnie
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Redilatation with intracameral mydriatics in phacoemulsification surgery.2006In: Acta Ophthalmologica Scandinavica, ISSN 1395-3907, E-ISSN 1600-0420, Vol. 84, no 1, p. 100-104Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To determine whether intracameral mydriatics can redilate pupils that contract during phacoemulsification cataract surgery. METHODS: A total of 80 patients were included in this prospective, randomized, double-blind study performed at Ornsköldsviks Hospital Eye Clinic. Of these, 60 patients had 0.6 microg/ml of epinephrine added to the balanced salt solution (BSS) used for irrigation and 20 patients did not. The patients in each group were randomized and given either an intracameral mydriatics (ICM) solution or placebo intracamerally after phacoemulsification and cortex cleaning. The pupil size was registered preoperatively, after cortex cleaning, 30 seconds after study injection, 2 mins after study injection and the day after surgery. RESULTS: No clinically relevant differences were found preoperatively. In the epinephrine material a significantly longer operation time (p = 0.023) and more procedures requiring Vision Blue and Kelman-type tip in the placebo group might indicate diversity in the grade of cataract. There was a greater degree of contraction in the absence of epinephrine in the irrigation solution (2.3 +/- 1.0 mm in the ICM group and 3.2 +/- 0.7 mm in the placebo group) compared to in the presence of epinephrine. With no epinephrine ICM significantly redilated the pupils at 30 seconds (p < or = 0.001) as well as at 2 mins (p = 0.015). CONCLUSION: We have shown that in cases with an intraoperative pupil contraction, ICM is effective in redilating the pupil. Insufficient adrenergic stimulation of the pupil dilator appears to be a major factor causing intraoperative pupil contraction during phacoemulsification cataract surgery.

  • 43. Celojevic, Dragana
    et al.
    Nilsson, Staffan
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Tasa, Gunnar
    Juronen, Erkki
    Karlsson, Jan-Olof
    Zetterberg, Henrik
    Petersen, Anne
    Zetterberg, Madeleine
    Superoxide dismutase gene polymorphisms in patients with age-related cataract2013In: Ophthalmic Genetics, ISSN 1381-6810, E-ISSN 1744-5094, Vol. 34, no 3, p. 140-145Article in journal (Refereed)
    Abstract [en]

    Background: Functional polymorphisms in genes encoding antioxidant enzymes may result in reduced enzyme activity and increased levels of reactive oxygen species, such as superoxide radicals, which in turn may contribute to increased risk of age-related disorders. Copper-zinc superoxide dismutases, SOD-1 and SOD-3, and manganese superoxide dismutase, SOD-2, are enzymes involved in the protection against oxidative stress and detoxification of superoxide. In this study, we investigated a number of disease-associated single nucleotide polymorphisms (SNPs) of SOD1, SOD2 and SOD3, in patients with age-related cataract.

    Materials and methods: The study included an Estonian sample of 492 patients with age-related cataract, subgrouped into nuclear, cortical, posterior subcapsular and mixed cataract, and 185 controls. Twelve SNPs in SOD1, SOD2 and SOD3 were genotyped using TaqMan Allelic Discrimination. Haplotype analysis was performed on the SNPs in SOD2.

    Results: None of the studied SNPs showed an association with risk of cataract. These results were consistent after adding known risk factors (age, sex and smoking) as covariates in the multivariate analyses and after stratification by cataract subtype. Analysis of SOD2 haplotypes did not show any associations with risk of cataract.

    Conclusions: If genetic variation in genes encoding SOD-1, SOD-2 and SOD-3 contributes to cataract formation, there is no major contribution of the SNPs analyzed in the present study.

  • 44.
    Chen, Jialin
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Chen, Peng
    Backman, Ludvig J.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Zhou, Qingjun
    Danielson, Patrik
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Ciliary Neurotrophic Factor Promotes the Migration of Corneal Epithelial Stem/progenitor Cells by Up-regulation of MMPs through the Phosphorylation of Akt2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 25870Article in journal (Refereed)
    Abstract [en]

    The migration of limbal epithelial stem cells is important for the homeostasis and regeneration of corneal epithelium. Ciliary neurotrophic factor (CNTF) has been found to promote corneal epithelial wound healing by activating corneal epithelial stem/progenitor cells. However, the possible effect of CNTF on the migration of corneal epithelial stem/progenitor cells is not clear. This study found the expression of CNTF in mouse corneal epithelial stem/progenitor cells (TKE2) to be up-regulated after injury, on both gene and protein level. CNTF promoted migration of TKE2 in a dose-dependent manner and the peak was seen at 10 ng/ml. The phosphorylation level of Akt (p-Akt), and the expression of MMP3 and MMP14, were up-regulated after CNTF treatment both in vitro and in vivo. Akt and MMP3 inhibitor treatment delayed the migration effect by CNTF. Finally, a decreased expression of MMP3 and MMP14 was observed when Akt inhibitor was applied both in vitro and in vivo. This study provides new insights into the role of CNTF on the migration of corneal epithelial stem/progenitor cells and its inherent mechanism of Up-regulation of matrix metalloproteinases through the Akt signalling pathway.

  • 45.
    Chen, Jialin
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Zhang, Wei
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Backman, Ludvig J.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Kelk, Peyman
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Danielson, Patrik
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Mechanical stress potentiates the differentiation of periodontal ligament stem cells into keratocytes2018In: British Journal of Ophthalmology, ISSN 0007-1161, E-ISSN 1468-2079, Vol. 102, no 4, p. 562-569Article in journal (Refereed)
    Abstract [en]

    Aims To explore the role of corneal-shaped static mechanical strain on the differentiation of human periodontal ligament stem cells (PDLSCs) into keratocytes and the possible synergistic effects of mechanics and inducing medium. Methods PDLSCs were exposed to 3% static dome-shaped mechanical strain in a Flexcell Tension System for 3 days and 7 days. Keratocyte phenotype was determined by gene expression of keratocyte markers. Keratocyte differentiation (inducing) medium was introduced in the Flexcell system, either continuously or intermittently combined with mechanical stimulation. The synergistic effects of mechanics and inducing medium on keratocyte differentiation was evaluated by gene and protein expression of keratocyte markers. Finally, a multilamellar cell sheet was assembled by seeding PDLSCs on a collagen membrane and inducing keratocyte differentiation. The transparency of the cell sheet was assessed, and typical markers of native human corneal stroma were evaluated by immunofluorescence staining. Results Dome-shaped mechanical stimulation promoted PDLSCs to differentiate into keratocytes, as shown by the upregulation of ALDH3A1, CD34, LUM, COL I and COL V. The expression of integrins were also upregulated after mechanical stimulation, including integrin alpha 1, alpha 2, beta 1 and non-muscle myosin II B. A synergistic effect of mechanics and inducing medium was found on keratocyte differentiation. The cell sheets were assembled under the treatment of mechanics and inducing medium simultaneously. The cell sheets were transparent, multilamellar and expressed typical markers of corneal stroma. Conclusion Dome-shaped mechanical stimulation promotes differentiation of PDLSCs into keratocytes and has synergistic effects with inducing medium. Multilamellar cell sheets that resemble native human corneal stroma show potential for future clinical applications.

  • 46. Claesson, Margareta
    et al.
    Armitage, W John
    Byström, Berit
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Montan, Per
    Samolov, Branka
    Stenvi, Ulf
    Lundström, Mats
    Validation of Catquest-9SF - A Visual Disability Instrument to Evaluate Patient Function After Corneal Transplantation2017In: Cornea, ISSN 0277-3740, E-ISSN 1536-4798, Vol. 36, no 9, p. 1083-1088Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Catquest-9SF is a 9-item visual disability questionnaire developed for evaluating patient-reported outcome measures after cataract surgery. The aim of this study was to use Rasch analysis to determine the responsiveness of Catquest-9SF for corneal transplant patients.

    METHODS: Patients who underwent corneal transplantation primarily to improve vision were included. One group (n = 199) completed the Catquest-9SF questionnaire before corneal transplantation and a second independent group (n = 199) completed the questionnaire 2 years after surgery. All patients were recorded in the Swedish Cornea Registry, which provided clinical and demographic data for the study. Winsteps software v.3.91.0 (Winsteps.com, Beaverton, OR) was used to assess the fit of the Catquest-9SF data to the Rasch model.

    RESULTS: Rasch analysis showed that Catquest-9SF applied to corneal transplant patients was unidimensional (infit range, 0.73-1.32; outfit range, 0.81-1.35), and therefore, measured a single underlying construct (visual disability). The Rasch model explained 68.5% of raw variance. The response categories of the 9-item questionnaire were ordered, and the category thresholds were well defined. Item difficulty matched the level of patients' ability (0.36 logit difference between the means). Precision in terms of person separation (3.09) and person reliability (0.91) was good. Differential item functioning was notable for only 1 item (satisfaction with vision), which had a differential item functioning contrast of 1.08 logit.

    CONCLUSIONS: Rasch analysis showed that Catquest-9SF is a valid instrument for measuring visual disability in patients who have undergone corneal transplantation primarily to improve vision.

  • 47.
    Claesson, Martin
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Johansson, Magdalena
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Mydriasis with different preparations of topically administered lidocaine hydrochloride2009In: Journal of cataract and refractive surgery, ISSN 0886-3350, E-ISSN 1873-4502, Vol. 35, no 2, p. 277-281Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To quantify the mydriatic effect and side effects of topical lidocaine hydrochloride with different pH values and concentrations in healthy volunteers.

    SETTING: Umeå University Hospital Eye Clinic, Umeå, Sweden.

    METHODS: In this intraindividual comparison double-masked randomized study, healthy volunteers were given topical lidocaine 8%, lidocaine 8% pH 6.0, or a placebo 3 times at 90-second intervals. Thereafter, a drop of tropicamide 0.5% or placebo was given (tropicamide setting). Another group of healthy volunteers was given topical lidocaine 4%, 8%, or 16% 3 or 6 times at 90-second intervals (dose-response setting). Before and 15, 30, 60, and 180 minutes after eyedrop instillation, the near point was determined and Scheimpflug photography was performed.

    RESULTS: The tropicamide setting comprised 26 volunteers (mean age 23.5 years) and the dose-response setting, 10 volunteers (mean age 24.5 years). The direct mydriatic effect of lidocaine was larger at pH 6.0 (mean peak effect 0.61+/-0.06 [SEM] versus 0.42+/-0.04 mm) (P< .05), and the augmentation of tropicamide mydriasis was larger at pH 6.0. Lidocaine 8% had a better direct mydriatic effect than lidocaine 4% and lidocaine 16% (mean peak effect 0.60+/-0.09 mm versus 0.19+/-0.08 mm and 0.28+/-0.10 mm, respectively) (P< .01). Lidocaine 16% given 6 times caused corneal side effects.

    CONCLUSIONS: Lidocaine 8% with pH 6.0 had a maximum direct mydriatic effect and gave maximum augmentation of tropicamide mydriasis without causing unwanted corneal side effects and thus should be preferable for topical anesthesia in cataract surgery.

  • 48. Czajka, Marcin Piotr
    et al.
    Byhr, Eva
    Olivestedt, Göran
    Olofsson, Eva M.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Endophthalmitis after small-gauge vitrectomy: a retrospective case series from Sweden2016In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 94, no 8, p. 829-835Article in journal (Refereed)
    Abstract [en]

    Purpose: To investigate the anatomical and functional outcomes of acute-onset endophthalmitis after small-gauge vitrectomy. Methods: Retrospective case series of patients who underwent 23- or 25-gauge vitrectomy at four centres in Sweden between 2008 and 2012. Postvitrectomy endophthalmitis was identified through the search of the journal records of each institution, and the diagnosis was based on clinical criteria regardless of culture results. Results: Twenty-four patients (24 eyes) were included. The incidence of endophthalmitis following small-gauge vitrectomy was 0.14%. Indications for small-gauge vitrectomy enclosed epiretinal membrane (n=13), retinal detachment (n=5) and others (n=6). Surgical technique included 23- and 25-gauge vitrectomy (23:1). Four eyes had sutured sclerotomies, and two had postoperative hypotony <7mmHg. Days to endophthalmitis presentation varied between 1 and 21 (mean 66). Treatment methods included the following: tap and antibiotic injection (n=7), tap, antibiotic injection with subsequent vitrectomy (n=2) and prompt vitrectomy with antibiotics (n=15). Sixteen eyes (66.7%) were culture positive, whereas the other eight cases were culture negative. Anatomical results included evisceration (n=1), phthisis (n=1), and globe intact (n=22). Presenting best corrected visual acuity (BCVA) were hand motion (n=14), light perception (n=7), counting fingers (n=2), and no data (n=1). Functionally 19 eyes (79%) had Snellen VA 0.1; 11 eyes (46%) had VA 0.5 Mean logMar BCVA preoperatively and at the last follow-up were 2.07 +/- 0.6 and 0.79 +/- 0.99, respectively. Conclusions: In spite of good anatomical and functional results, this study showed higher rate of endophthalmitis than the latest reports suggesting that small-gauge vitrectomy has reached the safety level of standard 20-gauge vitrectomy when infectious endophthalmitis is concerned.

  • 49. Di, Guohu
    et al.
    Qi, Xia
    Zhao, Xiaowen
    Zhang, Songmei
    Danielson, Patrik
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Zhou, Qingjun
    Corneal Epithelium-Derived Neurotrophic Factors Promote Nerve Regeneration2017In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 58, no 11, p. 4695-4702Article in journal (Refereed)
    Abstract [en]

    PURPOSE. To explore the neurotrophic factor expression in corneal epithelium and evaluate their effects on the trigeminal ganglion (TG) neurite outgrowth and corneal nerve regeneration in mice. METHODS. The expression of neurotrophic factors was compared among the intact, regenerating, and regenerated mouse corneal epithelium. Mouse primary TG neurons were treated with the conditioned medium of mouse corneal epithelial cells. Nerve growth factor (NGF) neutralizing antibody and glial cell-derived neurotrophic factor (GDNF) neutralizing antibody were used to evaluate their roles in mouse corneal nerve regeneration and TG neurite outgrowth. The promoting effects of NGF and GDNF for the corneal nerve regeneration were further evaluated in the diabetic mice. RESULTS. The expression of NGF and GDNF showed significant up-regulation in regenerating corneal epithelium and return to the preinjury levels in the regenerated epithelium, which was consistent with the progress of corneal subbasal nerve regeneration. The conditioned medium of corneal epithelial cells promoted the TG neurite outgrowth with extended branching and elongation. Furthermore, the blockage of either NGF or GDNF significantly impaired the promotion of the neurite outgrowth by the conditioned medium or the corneal nerve regeneration in normal mice. Moreover, the expression of NGF and GDNF was attenuated in the diabetic regenerating corneal epithelium as compared to that in normal mice, while exogenous NGF or GDNF supplement promoted the corneal epithelial and nerve regeneration in diabetic mice. CONCLUSIONS. Corneal epithelium expresses multiple neurotrophic factors, among which NGF and GDNF may play an important role in the corneal nerve regeneration.

  • 50.
    Eklund, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences.
    Bäcklund, Tomas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Andersson, Britt M
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Lindahl, Olof A
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Evaluation of applanation resonator sensors for intra-ocular pressure measurement: results from clinical and in vitro studies.2003In: Medical and Biological Engineering and Computing, ISSN 0140-0118, E-ISSN 1741-0444, Vol. 41, no 2, p. 190-197Article in journal (Refereed)
    Abstract [en]

    Glaucoma is an eye disease that, in its most common form, is characterised by high intra-ocular pressure (IOP), reduced visual field and optic nerve damage. For diagnostic purposes and for follow-up after treatment, it is important to have simple and reliable methods for measuring IOP. Recently, an applanation resonator sensor (ARS) for measuring IOP was introduced and evaluated using an in vitro pig-eye model. In the present study, the first clinical evaluation of the same probe has been carried out, with experiments in vivo on human eyes. There was a low but significant correlation between IOP(ARS) and the IOP measured with a Goldmann applanation tonometer (r = 0.40, p = 0.001, n = 72). However, off-centre positioning of the sensor against the cornea caused a non-negligible source of error. The sensor probe was redesigned to have a spherical, instead of flat, contact surface against the eye and was evaluated in the in vitro model. The new probe showed reduced sensitivity to off-centre positioning, with a decrease in relative deviation from 89% to 11% (1 mm radius). For normalised data, linear regression between IOP(ARS) and direct IOP measurement in the vitreous chamber showed a correlation of r = 0.97 (p < 0.001, n = 108) and a standard deviation for the residuals of SD < or = 2.18 mm Hg (n = 108). It was concluded that a spherical contact surface should be preferred and that further development towards a clinical instrument should focus on probe design and signal analysis.

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