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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.
    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)
  • 3.
    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.

  • 4. Aspberg, Johan
    et al.
    Heijl, Anders
    Jóhannesson, Gauti
    Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM). Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Linden, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Andersson-Geimer, Sabina
    Bengtsson, Boel
    Intraocular Pressure Lowering Effect of Latanoprost as First-line Treatment for Glaucoma2018In: Journal of glaucoma, ISSN 1057-0829, E-ISSN 1536-481X, Vol. 27, no 11, p. 976-980Article in journal (Refereed)
    Abstract [en]

    PURPOSE: The purpose of this study was to assess the intraocular pressure (IOP) - reducing effect of latanoprost in treatment-naïve patients with newly detected open-angle glaucoma with no restriction of the level of untreated IOP.

    METHODS: Eighty-six patients (105 eyes) with a diagnosis of open-angle glaucoma received IOP-lowering therapy with latanoprost. The IOP reduction 1 and 3 months after initiation of treatment was recorded.

    RESULTS: Mean untreated IOP for all eyes was 26.2 mm Hg (ranging from 10 to 51 mm Hg). The mean pressure reduction was 7.9 mm Hg (28%), with equivalent average levels at 1 and 3 months. The reduction in IOP ranged from -2.3 to 25.3 mm Hg after 1 month, and from -1.3 to 33.3 mm Hg after 3 months. The pressure-lowering effect was considerably more pronounced in eyes with higher untreated IOP; the reduction increased by 0.55 mm Hg per mm Hg higher untreated IOP. Four eyes, with untreated IOP within statistically normal limits, had no or negative IOP-reduction. A regression model predicted that IOP reduction ended at untreated IOP≤16 mm Hg. Multiple regression analysis showed that an additional IOP-lowering effect of 1.28 mm Hg was achieved in eyes with pseudoexfoliation glaucoma.

    CONCLUSIONS: To the best of our knowledge, this paper is the first to report the IOP-reducing effect of latanoprost treatment at all untreated IOP levels in newly detected glaucoma patients. The effect was proportional to the untreated IOP at all levels above 16 mm Hg and better at higher untreated IOP levels, also in relative terms. Our results further confirm the indication of latanoprost as a first-line therapy for glaucoma.

  • 5.
    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%.

  • 6.
    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.

  • 7.
    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.

  • 8.
    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.

  • 9.
    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.

  • 10.
    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.

  • 11. Bengtsson, Boel
    et al.
    Heijl, Anders
    Jóhannesson, Gauti
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Andersson-Geimer, Sabina
    Aspberg, Johan
    Linden, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    The Glaucoma Intensive Treatment Study (GITS), a randomized clinical trial: design, methodology and baseline data2018In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 96, no 6, p. 557-566Article in journal (Refereed)
    Abstract [en]

    Purpose: The primary objective of the ongoing Glaucoma Intensive Treatment Study (GITS) is to evaluate the effectiveness of immediate intensive treatment in comparison with the commonly recommended stepped regimen on the predicted visual field. The two treatment arms are also being compared regarding quality of life (QoL), intraocular pressure (IOP) reduction, frequency of reported side‐effects, adverse events and adherence to prescribed treatment.

    Design: A randomized, two‐centre, prospective open‐labelled treatment trial for open‐angle glaucoma.

    Participants: Individuals aged 40–78 years with previously untreated and newly diagnosed glaucoma with early to moderate visual field loss were eligible.

    Methods: Patients were randomized to initial treatment either using drug monotherapy in accordance with common glaucoma guidelines or using a more intensive approach including eyedrops containing drugs from three different classes combined with 360° laser trabeculoplasty. The patients are to be followed for 5 years at visits including standard automated perimetry, optical coherence tomography (OPT) and tonometry. Change of treatment is allowed and decided upon jointly with the patient as in conventional glaucoma management.Main outcome: The estimated predicted preserved visual field and QoL at end of expected lifetime.

    Results: A total of 242 patients, 45% females, mean age 68 years, were randomized. The median untreated IOP was 24 mm Hg, and the median visual field index (VFI), indicating the percentage of a full field, was 92%.

    Conclusion: Glaucoma Intensive Treatment Study is a clinical trial in which two groups of patients randomized to different initial intensities of IOP‐reducing treatment are being compared with regard to rate of visual field progression and prediction of serious glaucomatous visual field loss at estimated at end of life.

  • 12. Bengtsson, Boel
    et al.
    Linden, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Heijl, Anders
    Andersson-Geimer, Sabina
    Aspberg, Johan
    Jóhannesson, Gauti
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
    The glaucoma intensive treatment study: interim results from an ongoing longitudinal randomized clinical trial2022In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 100, no 2, p. e455-e462Article in journal (Refereed)
    Abstract [en]

    Purpose: The aim of the study was to determine the perimetric rate of glaucoma progression in the ongoing Glaucoma Intensive Treatment Study (GITS) after 3 years of follow-up.

    Design: This is a randomized, two-centre, prospective open-labelled treatment trial for open-angle glaucoma (OAG). Participants The participants of this study were treatment-naive patients with newly diagnosed OAG, aged 46-78 years, with early to moderate glaucomatous visual field loss scheduled to be followed for 5 years within the study.

    Methods: Patients were randomized to initial treatment with either topical monotherapy or with an intensive approach using drugs from three different classes, plus 360 degrees laser trabeculoplasty. Changes in treatment were allowed. Standard automated perimetry and tonometry were performed and side-effects documented. All results are presented using intention-to-treat analysis.

    Results: A total of 242 patients were randomized. After 3 years of follow-up, eight patients were lost to follow-up, six of whom were deceased. The median untreated baseline intraocular pressure (IOP) was 24 mmHg in both arms. The median IOP was almost constant over the 3 years of follow-up: approximate to 17 mmHg in the mono-arm and approximate to 14 mmHg in the multi-treatment arm. Treatment was intensified in 42% of the mono-treated patients and in 7% of the multi-treated patients. Treatment was reduced in 13% of the multi-treated patients. The median perimetric rate of progression was -0.5%/year in the mono-treated group and -0.1%/year in the multi-treated group (p = 0.03).

    Conclusion: The rate of disease progression was significantly slower in the multi-treated patients than in the mono-treated patients. Further follow-up will show whether this difference is sustained over time.

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  • 13.
    Bro, Tomas
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology. The Eye Department, Höglandssjukhuset, Eksjö.
    Linden, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    The More, the Better?: The Usefulness of Brimonidine as the Fourth Antiglaucoma Eye Drop2018In: Journal of glaucoma, ISSN 1057-0829, E-ISSN 1536-481X, Vol. 27, no 7, p. 643-646Article in journal (Refereed)
    Abstract [en]

    Purpose:The purpose of this article was to study the intraocular pressure (IOP)-lowering effect of adding brimonidine as the fourth antiglaucoma medication to a preexisting therapy of 3 topical drugs.

    Methods:This was a retrospective, register-based, cohort study of medical records and computerized medical information comprising 1 county in Sweden. The main outcome measure was change in IOP after brimonidine addition. Short-term and long-term effects were evaluated.

    Results:Of 4910 patients on antiglaucoma medication, 69 (1.4%) initiated a treatment with brimonidine as the fourth drug during 2014. Fifty-three patients were eligible for analysis. Forty-six patients tolerated the treatment. Among them, short-term IOP decreased by 17% (confidence interval, 10%-25%; P<0.001) after a mean of 46 days (SD, 50d). Twenty-eight patients, that is, 53% of the eligible, remained on unchanged therapy after a mean follow-up time of 368 days (SD, 61d). The long-term mean IOP decrease in this group was 20% (confidence interval, 11%-29%; P<0.0001). An IOP reduction of at least 20% was reached by 28 and 14 patients, in the short-term and long-term follow-ups, respectively.

    Conclusions:Brimonidine has the potential to reduce the IOP significantly even when used as the fourth drug. In the short-term, half of the patients reached the target IOP reduction (20%). After 1 year, a quarter of the eligible patients had had a sustained, uneventful effect. Thus, brimonidine as the fourth adjunctive antiglaucoma drop seems a valuable option for a minority of patients.

  • 14.
    Bro, Tomas
    et al.
    Department of Ophthalmology, Eksjö, Sweden; Section for Ophthalmology, Department of Clinical Sciences, Lund University, Lund, Sweden.
    Wickström, Kerstin
    Icelandic Medicines Agency, Reykjavik, Iceland.
    Linden, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    The future is old: patients with topical ocular hypotensive treatment in the Nordic region between 2008 and 2017 with projections for 20402021In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 99, no 2, p. e1442-e1448Article in journal (Refereed)
    Abstract [en]

    Purpose: The primary objective was to evaluate prescribing trends for topical ocular hypotensive treatment in the Nordic region during the last decade and, by population projections, estimate the glaucoma burden in 2040. A secondary objective was to analyse national variations in prescription patterns across the Nordic region.

    Methods: A retrospective analysis of national pharmacy data between 2008 and 2017 on the dispensation of topical ocular hypotensive treatment in the Nordic region was performed. Predictions of the glaucoma burden in 2040 were calculated from official population projections.

    Results: The total number of patients with ocular hypotensive treatment in the Nordic region increased from 346 000 to 418 000 (21%) between 2008 and 2017. The number of patients with ocular hypotensive treatment in the age group of 50 years and older increased from 3.6% to 3.9%. The daily defined dose (DDD) per patient and day during the study period increased from 1.22 to 1.26. Adjusted for beta-blocker combinations, the same value increased from 1.49 to 1.67. Across the Nordic countries, Finland had almost twice as many DDD per patient and day in 2017 (2.1) compared with Iceland (1.1). Between 2008 and 2017, the annual treatment cost for ocular hypotensive treatment in the Nordic region decreased from 96 million to 87 million Euro (−9%). In 2040, the number of patients with ocular hypotensive treatment in the Nordic region is estimated to 633 000 individuals (+51% compared with 2017).

    Conclusions: The study revealed an increased use of glaucoma medications in the Nordic region the last decade. This was mainly caused by an increased number of patients with ocular hypotensive treatment, but also because of a more intensive treatment. Marked national differences were detected. Due to the introduction of generic medications, the total cost for ocular hypotensive treatment did however decrease during the last decade. In 2040, the current number of individuals with ocular hypotensive treatment is estimated to have increased with an additional 50% due to a growing number of ageing individuals. This will lead to higher costs, not only for medications but also for diagnosing, monitoring and other aspects of glaucoma care.

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  • 15.
    Byström, Berit
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Virtanen, Ismo
    Rousselle, Patricia
    Miyazaki, Kaoru
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Pedrosa-Domellöf, Fatima
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Laminins in normal, keratoconus, bullous keratopathy and scarred human corneas2007In: Histochemistry and Cell Biology, ISSN 0948-6143, E-ISSN 1432-119X, Vol. 127, no 6, p. 657-667Article in journal (Refereed)
    Abstract [en]

    The laminin composition (LMalpha1-alpha5, beta1-beta3, gamma1 and gamma2 chains) of normal corneas and corneal buttons from keratoconus, bullous keratopathy (BKP), Fuchs' dystrophy + BKP, Fuchs' dystrophy without BKP and scar after deep lamellar keratoplasty (DLKP) was investigated with immunohistochemistry. The epithelial basement membranes (BMs) of both normal and diseased corneas contained LMalpha3, alpha5, beta1, beta3, gamma1 and gamma2 chains. The epithelial BM morphology was altered in the different diseases. Scarring was associated with irregular BM and ectopic stromal localization of different laminin chains. The Descemet's membrane (DM) contained LMalpha5, beta1 and gamma1 chains in all cases and additionally LMbeta3 and gamma2 chains in the majority of keratoconus corneas. The interface in the DLKP cornea had patches of LMalpha3, alpha4, alpha5, beta1 and beta2 chains, and an extra BM-like structure under the Bowman's membrane. These results suggest that laminin chains participate in the process of corneal scarring and in the pathogenesis of some corneal diseases. The novel finding of LMalpha3, beta3 and gamma2 in the DM of keratoconus buttons indicates that this membrane is also involved in the disease and that some cases of keratoconus may have a congenital origin, without normal downregulation of the LMbeta3 chain.

  • 16.
    Eklund, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Hallberg, Per
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Lindahl, Olof A.
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    An applanation resonator sensor for measuring intraocular pressure using combined continuous force and area measurement2003In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 44, no 7, p. 3017-3024Article in journal (Refereed)
  • 17.
    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.

  • 18.
    Gustavsson, Simon T.
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Enz, Tim J.
    Department of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden; Department of Ophthalmology, University of Basel, Basel, Switzerland.
    Tribble, James R.
    Department of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden.
    Nilsson, Mattias
    Department of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden.
    Lindqvist, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Linden, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Hagström, Anna
    Department of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden.
    Rutigliani, Carola
    Department of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden.
    Lardner, Emma
    Department of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden.
    Stålhammar, Gustav
    Department of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden.
    Williams, Pete A.
    Department of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, Eugeniavägen 12, Solna, Sweden.
    Jóhannesson, Gauti
    Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM). Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology. Department of Ophthalmology, University of Iceland, Iceland.
    Nicotinamide prevents retinal vascular dropout in a rat model of ocular hypertension and supports ocular blood supply in glaucoma patients2023In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 64, article id 34Article in journal (Refereed)
    Abstract [en]

    PURPOSE. To investigate whether nicotinamide (NAM) modulates retinal vasculature in glaucoma.

    METHODS. This was a prospective controlled clinical trial investigating animal and human histopathology. Participants included normotensive and ocular hypertensive rats, postmortem human ocular tissue, glaucoma patients (n = 90), and healthy controls (n = 30). The study utilized histopathology, computer-assisted retinal vasculature analysis, optical coherence tomography angiography (OCTA), and NAM treatment. The main outcome measures included retinal vascular parameters in rats as assessed by AngioTool; retinal vasculature integrity in rats and humans as assessed by histopathology, antibody-staining, and ImageJ-based measurements; and retinal perfusion density (PD) and flux index in humans as assessed by OCTA.

    RESULTS. A number of vessel parameters were altered in ocular hypertension/glaucoma compared to healthy controls. NAM treatment improved the retinal vasculature in ocular hypertensive rats, with an increase in mean vessel area, percentage area covered by vessels, total vessel length, total junctions, and junction density as assessed by AngioTool (all P < 0.05); vessel wall integrity as assessed by VE-cadherin antibody staining was also improved (P < 0.01). In humans, as assessed by OCTA, increases in PD in the optic nerve head and macula complete image (0.7%, P = 0.04 and 1.0%, P = 0.002, respectively) in healthy controls, and an increase in the temporal quadrant of the macula (0.7%, P = 0.02) in glaucoma patients was seen after NAM treatment.

    CONCLUSIONS. NAM can prevent retinal vascular damage in an animal model of glaucoma. After NAM treatment, glaucoma patients and healthy controls demonstrated a small increase in retinal vessel parameters as assessed by OCTA.

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  • 19. Hallberg, Per
    et al.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Bäcklund, Tomas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Clinical evaluation of applanation resonance tonometry: a comparison with Goldmann applanation tonometry.2007In: Journal of glaucoma, ISSN 1057-0829, E-ISSN 1536-481X, Vol. 16, no 1, p. 88-93Article in journal (Refereed)
    Abstract [en]

    PURPOSE: The purpose of this study was to calibrate and evaluate the precision of the new applanation resonance tonometry (ART) in a clinical study designed in accordance with the International Standard Organization's requirements. METHODS: This was a prospective, randomized, single-center study, where healthy volunteers and patients participated. A total of 153 eyes were divided into 3 groups with respect to their intraocular pressure (IOP) at screening: <16 mm Hg, 16 to 23 mm Hg, and >23 mm Hg. IOP was measured with Goldmann applanation tonometry (GAT) as reference method and by ART in both a biomicroscope (ARTBiom) and a handheld (ARTHand) setup with a 10-minutes pause between methods. The mean of 6 readings was regarded as one measurement value. RESULTS: Mean age of the subjects was 59 years (range 20 to 87 y). GAT showed a mean IOP of 20.0 mm Hg (range 8.5 to 43.5 mm Hg, n=153). The precision was 2.07 mm Hg for ARTBiom and 2.50 mm Hg for ARTHand, with a significant dependency for age as compared with GAT. Measurement order produced a decreasing IOP with a mean of 2.3 mm Hg between the first and last method. CONCLUSIONS: The precision obtained in both ARTBiom and ARTHand was within the limits set by the International Standard Organization standards for tonometers. The standardized procedure and the stability of the biomicroscope setup resulted in a slightly better precision as compared with the handheld setup. Despite a 10-minutes pause between measurements, the order was a significant factor, possibly because the patients were more apprehensive at the first measurement.

  • 20.
    Hallberg, Per
    et al.
    Department of Biomedical Engineering and Informatics, University Hospital, Umeå, Sweden.
    Eklund, Anders
    Department of Biomedical Engineering and Informatics, University Hospital, Umeå, Sweden.
    Santala, Kenneth
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Koskela, Timo
    Lindahl, Olof A.
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Underestimation of intraocular pressure after photorefractive keratectomy: a biomechanical analysis2006In: Medical and Biological Engineering and Computing, ISSN 0140-0118, E-ISSN 1741-0444, Vol. 44, p. 609-618Article in journal (Refereed)
    Abstract [en]

    Excimer laser surgery, to correct corneal refraction, induces changes in corneal thickness and curvature. Both factors can cause measurement errors when determining intraocular pressure (IOP). This study evaluates effects of photorefractive keratectomy (PRK) on IOP measurements, using Goldmann applanation tonometry (GAT) and Applanation resonance tonometry (ART), in an in vitro model. Six porcine eyes was enucleated and pressurised to a constant IOP = 30 mmHg. After removal of the epithelium, the eyes were PRK-treated for a total of 25 dioptres. The measured IOP decreased 13.2 mmHg for GAT and 9.0 mmHg for ART. The total underestimation by GAT was larger than for ART, and a part of the ART underestimation (3.5 mmHg) was assigned to sensitivity to the change in corneal surface structure resulting from the removal of epithelium. The flat contact probe of GAT, as compared with the convex tip of ART, provided explanation for the difference in IOP measurement error after PRK.

  • 21.
    Hallberg, Per
    et al.
    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).
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Bäcklund, Tomas
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Symmetric sensor for applanation resonance tonometry of the eye2006In: Medical and Biological Engineering and Computing, ISSN 0140-0118, E-ISSN 1741-0444, Vol. 44, no 1-2, p. 54-60Article in journal (Refereed)
    Abstract [en]

    Applanation resonance tonometry (ART) has been shown in a number of studies to be useful for measuring intraocular pressure (IOP). Data from in vitro laboratory bench testing, where the sensor was carefully centralised onto the cornea, has been very consistent with good precision in the determination of IOP. However, in a clinical study the unavoidable off-centre placement of the sensor against the cornea resulted in a reduced precision. The aim of this study was to evaluate a new design of the sensor with a symmetric sensor probe and a contact piece with a larger diameter. Two in vitro porcine eye experimental set-ups were used. One bench-based for examining position dependence and one biomicroscope-based set-up, simulating a clinical setting, for evaluating IOP(ART) precision at seven different pressure levels (1040 mmHg), set by connecting a saline column to the vitreous chamber. The reference IOP was recorded using a pressure transducer. There was no significant difference between four positions 1 mm off centre and the one centre position. The precision of the ART as compared with the reference pressure was +/- 1.03 mmHg (SD, n = 42). The design improvement has enhanced the precision of the ART in the biomicroscope set-up to be in parity with bench test results from a set-up using perfect positioning. This indicates that off-centre positioning was no longer a major contributor to the deviations in measured IOP. The precision was well within the limits set by ISO standard for eye tonometers. Therefore, a larger in vivo study on human eyes with the ART should be performed.

  • 22.
    Hallberg, Per
    et al.
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    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).
    Bäcklund, Tomas
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Eklund, Anders
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Applanation resonance tonometry for intraocular pressure in humans2004In: Physiological Measurement, ISSN 0967-3334, E-ISSN 1361-6579, Vol. 25, no 4, p. 1053-1065Article in journal (Refereed)
    Abstract [en]

    Glaucoma is a group of diseases associated with optic nerve damage and loss of visual field. The aetiology is not completely understood, but one of the major risk factors is elevated intraocular pressure (IOP). Reliable methods for measuring the IOP are therefore important. The aim of the study was to investigate the ability of the applanation resonance tonometry (ART) system, based on continuous force and area recording, to measure IOP in humans. Both the phase of initial indentation (IOPIndentation) and the phase when the sensor was removed (IOPRemoval) from the cornea were analysed. The Goldmann applanation tonometry (GAT) was used as reference method. The study included 24 healthy volunteers with normal IOP and 24 patients with elevated IOP. The correlation and standard deviation (SD) between IOPIndentation and IOPGAT was R = 0.92 (p < 0.001), SD = 3.6 mmHg, n = 104, and between IOPRemoval and IOPGAT R = 0.94 (p < 0.001), SD = 3.1 mmHg, n = 104. In conclusion, resonance sensor technology has made it possible to introduce a new multi-point method for measuring IOP, and the method is relevant for measuring IOP in humans. The study indicates that with further development towards elimination of position dependence, the ART has the potential to become a useful clinical instrument for IOP measurement.

  • 23.
    Hallberg, Per
    et al.
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Santala, Kenneth
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Lindahl, Olof A
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF). Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Comparison of Goldmann applanation and applanation resonance tonometry in a biomicroscope-based in vitro porcine eye model2006In: J Med Eng Technol, ISSN 0309-1902, Vol. 30, no 6, p. 345-352Article in journal (Refereed)
  • 24.
    Heijl, Anders
    et al.
    Skånes universitetssjukhus, Malmö.
    Alm, Albert
    Neurovetenskap, Ögon, Uppsala.
    Bengtsson, Boel
    Skånes universitetssjukhus, Malmö.
    Bergström, Anders
    Ögonkliniken Skånes universitetssjukhus, Malmö-Lund.
    Calissendorff, Berit
    S:t Eriks ögonsjukhus, Stockholm.
    Lindblom, Bertil
    Inst f neurovetenskaper, Sahlgrenska Akademin, Göteborgs universitet.
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Riktlinjer för glaukomsjukvården2010Book (Refereed)
  • 25.
    Heijl, Anders
    et al.
    Department of Ophthalmology Skåne University Hospital Malmö, Malmö, Sweden .
    Alm, Albert
    Department of Ophthalmology, Academic Hospital, Uppsala, Sweden.
    Bengtsson, Boel
    Clinical Sciences Malmö, Department of Ophthalmology, Lund University, Lund, Sweden .
    Bergström, Anders
    Department of Ophthalmology, Skåne University Hospital Malmö-Lund, Sweden.
    Calissendorff, Berit
    St. Erik Eye Hospital, Stockholm, Sweden.
    Lindblom, Bertil
    Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    The Glaucoma Guidelines of the Swedish Ophthalmological Society2012In: Acta ophthalmologica. Supplement, ISSN 1755-375X, no 251, p. 1-40Article in journal (Refereed)
  • 26.
    Heijl, Anders
    et al.
    Ogonkliniken, Skånes universitetssjukhus, Malmö.
    Alm, Albert
    Neurovetenskap, Ögon, Uppsala.
    Bengtsson, Boel
    Lund.
    Calissendorf, Berit
    Linden, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Eckerlund, Ingemar
    Öppenvinkelglaukom: diagnostik, uppföljning och behandling: En systematisk litteraturöversikt från SBU2010In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 107, no 19-20, p. 1311-1313Article in journal (Refereed)
    Abstract [sv]

    Sänkning av ögontrycket fördröjer synfältsförsämringen vid glaukom och minskar risken för utveckling av glaukom vid okulär hypertension.

    Det är oklart om laserbehandling eller kirurgi är bättre än behandling med ögondroppar.

    Modern, snabb synfältstestning har hög diagnostisk träffsäkerhet (sensitivitet och specificitet).

    Diagnostik baserad på expertbedömning av papillfoton har låg till måttligt hög diagnostisk träffsäkerhet.

    Moderna instrument baserade på datoriserad bildanalys har likvärdig diagnostisk träffsäkerhet.

    Särskild uppmärksamhet bör ägnas åt att säkerställa att gruppen glaukompatienter inte eftersätts i sjukvården.

    Behandlingen av glaukom och uppföljningen behöver individualiseras i ökad omfattning.

    Synfältsundersökning bör göras mer frekvent de första åren efter diagnos.

  • 27.
    Johannesson, Gauti
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Hallberg, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Ambarki, Khalid
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Eklund, Anders
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Linden, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Age-dependency of ocular parameters - a cross sectional study of young and old healthy subjects2015In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 56, no 7, article id Meeting Abstract: 116Article in journal (Other academic)
    Abstract [en]

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

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

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

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

  • 28.
    Johannesson, Gauti
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Hallberg, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Ambarki, Khalid
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Eklund, Anders
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Linden, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Age-dependency of ocular parameters: a cross sectional study of young and elderly healthy subjects2015In: Graefe's Archives for Clinical and Experimental Ophthalmology, ISSN 0721-832X, E-ISSN 1435-702X, Vol. 253, no 11, p. 1979-1983Article in journal (Refereed)
    Abstract [en]

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

  • 29.
    Johannesson, Gauti
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Hallberg, Per
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Linden, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Effects of topical anaesthetics and repeated tonometry on intraocular pressure2014In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 92, no 2, p. 111-115Article in journal (Refereed)
    Abstract [en]

    Purpose:

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

    Methods:

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

    Results:

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

    Conclusion:

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

  • 30.
    Johannesson, Gauti
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Hallberg, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Koskela, Timo
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Linden, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Change in intraocular pressure measurement 2 years after myopic laser-assisted subepithelial keratectomy2012In: Journal of cataract and refractive surgery, ISSN 0886-3350, E-ISSN 1873-4502, Vol. 38, no 9, p. 1637-1642Article in journal (Refereed)
    Abstract [en]

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

  • 31.
    Jóhannesson, Gauti
    et al.
    Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM). Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Linden, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Intracranial and Intraocular Pressure at the Lamina Cribrosa: Gradient Effects2018In: Current Neurology and Neuroscience Reports, ISSN 1528-4042, E-ISSN 1534-6293, Vol. 18, no 5, article id 25Article, review/survey (Refereed)
    Abstract [en]

    Purpose of Review: A pressure difference between the intraocular and intracranial compartments at the site of the lamina cribrosa has been hypothesized to have a pathophysiological role in several optic nerve head diseases. This paper reviews the current literature on the translamina cribrosa pressure difference (TLCPD), the associated pressure gradient, and its potential pathophysiological role, as well as the methodology to assess TLCPD.

    Recent Findings: For normal-tension glaucoma (NTG), initial studies indicated low intracranial pressure (ICP) while recent findings indicate that a reduced ICP is not mandatory.

    Summary: Data from studies on the elevated TLCPD as a pathophysiological factor of NTG are equivocal. From the identification of potential postural effects on the cerebrospinal fluid (CSF) communication between the intracranial and retrolaminar space, we hypothesize that the missing link could be a dysfunction of an occlusion mechanism of the optic nerve sheath around the optic nerve. In upright posture, this could cause an elevated TLCPD even with normal ICP and we suggest that this should be investigated as a pathophysiological component in NTG patients.

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  • 32.
    Jóhannesson, Gauti
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Gudmundsdóttir, Gudrún J
    Rejykjavik, Island.
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Can the prevalence of open-angle glaucoma be estimated from a retrospective clinical material? A study on the west coast of Iceland.2005In: Acta Ophthalmologica Scandinavica, ISSN 1395-3907, E-ISSN 1600-0420, Vol. 83, no 5, p. 549-553Article in journal (Refereed)
    Abstract [en]

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

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

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

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

  • 33.
    Jóhannesson, Gauti
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Hallberg, Per
    Eklund, Anders
    Koskela, Timo
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Change in intraocular pressure measurement after myopic LASEK: a study evaluating Goldmann, Pascal and applanation resonance tonometry2012In: Journal of glaucoma, ISSN 1057-0829, E-ISSN 1536-481X, Vol. 21, no 4, p. 255-259Article in journal (Refereed)
    Abstract [en]

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

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

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

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

  • 34.
    Jóhannesson, Gauti
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Hallberg, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Introduction and clinical evaluation of servo-controlled applanation resonance tonometry2012In: Acta Ophthalmologica Scandinavica, ISSN 1395-3907, E-ISSN 1600-0420, Vol. 90, no 7, p. 677-682Article in journal (Refereed)
    Abstract [en]

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

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

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

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

  • 35.
    Jóhannesson, Gauti
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Hallberg, Per
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Pascal, ICare and Goldmann applanation tonometry: a comparative study2008In: Acta ophthalmologica, ISSN 1755-3768, Vol. 86, no 6, p. 614-621Article in journal (Refereed)
    Abstract [en]

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

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

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

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

  • 36.
    Jóhannesson, Gauti
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Hallberg, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Can we trust intraocular pressure measurements in eyes with intracameral air?2014In: Graefe's Archives for Clinical and Experimental Ophthalmology, ISSN 0721-832X, E-ISSN 1435-702X, Vol. 252, no 10, p. 1607-1610Article in journal (Refereed)
    Abstract [en]

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

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

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

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

  • 37.
    Jóhannesson, Gauti
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
    Qvarlander, Sara
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    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). Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Ambarki, Khalid
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Hallberg, Per
    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).
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Intraocular Pressure Decrease Does Not Affect Blood Flow Rate of Ophthalmic Artery in Ocular Hypertension2020In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 61, no 12, article id 17Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To investigate if decrease of IOP affects the volumetric blood flow rate in the ophthalmic artery (OA) in patients with previously untreated ocular hypertension.

    METHODS: Subjects with untreated ocular hypertension (n = 30; mean age 67 +/- 8 years; 14 females) underwent ophthalmologic examination and a 3-Tesla magnetic resonance imaging investigation. The magnetic resonance imaging included three-dimensional high-resolution phase-contrast magnetic resonance imaging to measure the OA blood flow rate. The subjects received latanoprost once daily in the eye with higher pressure, the untreated eye served as control. The same measurements were repeated approximately 1 week later.

    RESULTS: The mean OA blood flow rate before and after treatment was 12.4 +/- 4.4 and 12.4 +/- 4.6 mL/min in the treated eye (mean +/- SD; P = 0.92) and 13.5 +/- 5.2 and 13.4 +/- 4.1 mL/min in the control eye (P = 0.92). There was no significant difference between the treated and control eye regarding blood flow rate before (P = 0.13) or after treatment (P = 0.18), or change in blood flow rate after treatment (0.1 +/- 3.1 vs.-0.1 +/- 4.0 mL/min, P = 0.84). Latanoprost decreased the IOP by 7.2 +/- 3.1 mm Hg in the treated eye (P < 0.01).

    CONCLUSIONS: The results indicate that a significant lowering of IOP does not affect the blood flow rate of the OA in ocular hypertension subjects. The ability to maintain blood supply to the eye independent of the IOP could be a protective mechanism in preserving vision in subjects with ocular hypertension.

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  • 38.
    Jóhannesson, Gauti
    et al.
    Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM). Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology. Department of Ophthalmology, University of Iceland, Reykjavik, Iceland.
    Stille, Ulf
    Department of Ophthalmology, Falu Lasarett, Falun, Sweden.
    Taube, Amelie Botling
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Karlsson, Markus
    Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
    Kalaboukhova, Lada
    Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Bergström, Anders
    Department of Clinical Sciences, Ophthalmology, Lund University, Lund, Sweden.
    Peters, Dorothea
    Department of Clinical Sciences, Ophthalmology, Lund University, Malmö, Sweden.
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Guidelines for the management of open-angle glaucoma: national program area eye diseases, national working group glaucoma2024In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 102, no 2, p. 135-150Article in journal (Refereed)
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  • 39.
    Kobelt, Gisela
    et al.
    European Health Economics, Spéracèdes, France.
    Jonsson, Björn
    Bergström, Anders
    Chen, Enping
    Karolinska institutet, S:t Eriks ögonsjukhus.
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Alm, Albert
    Uppsala universitet, medicinska fakulteten.
    Cost-effectiveness analysis in glaucoma: what drives utility? Results from a pilot study in Sweden.2006In: Acta Ophthalmologica Scandinavica, ISSN 1395-3907, E-ISSN 1600-0420, Vol. 84, no 3, p. 363-71Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To investigate the effect of different levels of visual field defect in glaucoma on utilities and to test if utilities could be assessed using a general questionnaire such as the EQ-5D. METHODS: A cross-sectional study in 199 patients with ocular hypertension or open-angle glaucoma grouped into 5 severity stages according to visual field defects was performed in 4 specialized ophthalmic centres. Descriptive analysis was performed for the sample and by stage, and the effect of vision loss on utility was investigated with multiple step-wise regression analysis. RESULTS: The mean age of the sample was 70 and the mean MD in the worse eye was -13.1 dB (SD 10.2). Visual acuity (VA) was 0.63 and 0.87 in the worse and better eye, respectively, and the mean utility was 0.80 (SD 0.23). Utility decreased with increasing glaucomatous damage, ranging from 0.84 for mild disease to 0.72 for severe damage (MD -2.5 to -28.1), but the difference between the groups was not statistically significant when controlling for co-morbidity, except for the most severe stage (p < 0.01). In multiple regression analysis, visual field in the better eye was significantly correlated with utility, and there was an indirect correlation between visual field in the worse eye and utility: the effect of total VA on utility was significant, and MD in the worse eye was correlated with total VA. CONCLUSIONS: Utility is strongly correlated with overall vision. Our results suggest a relationship between glaucomatous damage and utility, and patients with severe damage have a significantly lower utility. However, this should be further investigated in larger samples that include more patients with moderate-severe bilateral damage.

  • 40.
    Krachler, Benno
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Jerdén, L.
    Center for Clinical Research Dalarna-Uppsala University, Falun, Sweden; School of Education, Health and Social Studies, Dalarna University, Falun, Sweden.
    Tönnesen, H.
    Clinical Health Promotion Centre, WHO-CC, Region Skåne and Department of Health Sciences, Faculty of Medicine, Lund University, Sweden.
    Linden, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Medical licensing examinations in both Sweden and the US favor pharmacology over lifestyle2021In: Preventive Medicine Reports, E-ISSN 2211-3355, Vol. 23, article id 101453Article in journal (Refereed)
    Abstract [en]

    Low priority of disease prevention and health promotion in medical education may contribute to lack of lifestyle-counseling in clinical practice. Pharmacology-related knowledge is valued 5 times higher compared to lifestyle-related knowledge in examinations on noncommunicable diseases (NCDs) in undergraduate medical education in Sweden. This study aims to establish (i) whether medical licensing examinations are biased to favor pharmacology- over lifestyle-related knowledge and (ii) whether such a bias is present in both Sweden and the US.

    We identified 204 NCD-related questions from previous Swedish licensing examinations, and 77 cases from a U.S. question bank commonly used to prepare for the United States Medical Licensing Examination® (USMLE®) Step 3. With the help of expected correct answers, we determined distribution of points attainable for knowledge in the respective category (lifestyle / pharmacology / other) for 5 major NCDs: coronary heart disease (CHD), chronic obstructive pulmonary disease (COPD), diabetes, hypertension, and stroke.

    The percentage of points attainable for lifestyle-related knowledge was 6.7 (95% CI 4.1–9.3) in Sweden and 4.6 (95%CI 0.0–9.1) in the U.S. The respective percentages for pharmacology-related knowledge were 32.6 (95% CI 26.3–38.8) and 44.5 (95% CI 33.2–55.8) percent. The pharmacology vs. lifestyle-quotas were 4.9 in Sweden and 9.8 in the U.S. Likelihoods of equal emphasis on lifestyle and pharmacology in NCDs was < 0.001 in both countries.

    There is a marked preference for pharmacology over lifestyle in medical licensing examinations in both Sweden and the U.S. Newly qualified doctors may be inadequately prepared to address preventable causes of NCDs.

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  • 41.
    Krachler, Benno
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Jerdén, Lars
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Kunskap om levnadsvanor värderas olika på läkarutbildningarna: en genomgång av 124 skriftliga examinationer2018In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 115, article id EWPDArticle in journal (Refereed)
    Abstract [en]

    Lifestyle factors are crucial for prevention and management of many non-communicable diseases such as hypertension, stroke, diabetes, coronary heart disease and chronic obstructive pulmonary disease. Lifestyle medicine is included in national learning outcomes for undergraduate medical education in Sweden. Since assessment drives learning, we reviewed questions from 124 written examinations from all 7 medical schools in Sweden, conducted between 2012 and 2015. There is up to a 5-fold difference between different universities in the weight attached to lifestyle-related knowledge compared to knowledge related to pharmacological treatments.

  • 42.
    Krachler, Benno
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Jerdén, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Written examinations in Swedish medical schools: minds molded to medicate?2019In: American Journal of Lifestyle Medicine, ISSN 1559-8276, E-ISSN 1559-8284, Vol. 13, no 6, p. 611-614Article in journal (Refereed)
    Abstract [en]

    Lifestyle medicine (LM) is part of official educational goals in Swedish medical schools. We studied questions concerning 5 noncommunicable diseases: diabetes, hypertension, coronary heart disease (CHD), chronic obstructive pulmonary disease (COPD), and stroke from 124 written examinations conducted between 2012 and 2015. LM knowledge yielded between 2% and 10%, whereas pharmacology-related knowledge yielded between 24% and 50%, of total points. The multiples at which pharmacology-related knowledge was valued higher than LM knowledge were 2.4 for COPD (P < .056), 4.3 for diabetes (P < .0001), 4.8 for hypertension (P < .0001), 5.2 for CHD (P < .0001), and 31.5 for stroke (P < .0001). Our results indicate that lifestyle-related knowledge, though covered by official teaching goals, is currently underrated in Swedish medical education.

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  • 43.
    Kristiansen, Martin
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Holmlund, Petter
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Linden, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Jóhannesson, Gauti
    Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM). Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology. Department of Ophthalmology, University of Iceland, Reykjavik, Iceland.
    Author response: deficient optic nerve sheath occlusion in ntg patients: optic nerve damage due to translaminar pressure imbalance, glymphatic failure, or both?2024In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 65, no 5, article id 19Article in journal (Other academic)
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  • 44.
    Kristiansen, Martin
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Holmlund, Petter
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Linden, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Jóhannesson, Gauti
    Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM). Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology. Department of Ophthalmology, University of Iceland, Reykjavik, Iceland.
    Optic nerve subarachnoid space posture dependency: an MRI study in subjects with normal tension glaucoma and healthy controls2023In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 64, no 15, article id 20Article in journal (Refereed)
    Abstract [en]

    Purpose: The purpose of this study was to examine the differences of optic nerve subarachnoid space (ONSAS) volume in patients with normal tension glaucoma (NTG) and healthy controls in different body positions.

    Methods: Eight patients with NTG and seven healthy controls underwent magnetic resonance imaging (MRI) examinations in head up tilt (HUT) +11 degrees and head down tilt (HDT) -5 degrees positions according to a randomized protocol determining the starting position. The ONSAS volume in both body positions was measured and compared between the two groups. The results were analyzed using a generalized linear model.

    Results: Between HDT and HUT, the postural ONSAS volume change was dependent on starting position (P < 0.001) and group (P = 0.003, NTG versus healthy). A subgroup analysis of those that were randomized to HUT examination first, coming directly from an upright position, showed that the patients with NTG had significantly larger positional ONSAS volume changes compared to the healthy controls; 121 ± 22 µL vs. 65 ± 37 µL (P = 0.049). Analysis of the ONSAS volume distribution showed different profiles for patients with NTG and healthy controls.

    Conclusions: There was a significant difference in ONSAS volume change between patients with NTG and healthy subjects when subjected to posture changes, specifically when going from upright to head-down posture. This indicates that patients with NTG had been exposed to a lower ONSAS pressure when they came from the upright posture, which suggests an increased translaminar pressure difference in upright position. This may support the theory that NTG has a dysfunction in an occlusion mechanism of the optic nerve sheath that could cause abnormally negative ONSAS pressures in upright posture.

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  • 45.
    Kristiansen, Martin
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Linden, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Qvarlander, Sara
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Wåhlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Ambarki, Khalid
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Hallberg, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Jóhannesson, Gauti
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Blood flow rate of ophthalmic artery in patients with normal tension glaucoma and healthy controls2018In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 59, no 9Article in journal (Other academic)
    Abstract [en]

    Purpose: To determine the blood flow rate of the ophthalmic artery (OA) in patients with Normal Tension Glaucoma (NTG) compared to age-matched healthy controls using phase-contrast magnetic resonance imaging (PCMRI).

    Methods: Seventeen patients with treated NTG (11 female; mean age: 70±9 years) and 16 age-matched healthy controls (10 female; mean age: 71±9 years) underwent PCMRI using a 3-Tesla scanner as well as ophthalmological examinations including visual acuity, Goldmann Applanation Tonometry, Humphrey perimetry and fundoscopy. Ophthalmic blood flow was acquired using a 2D PCMRI sequence set to a spatial resolution of 0.35mm/pixel. Mean flow rate and cross-sectional area was calculated using Segment Software. The eye with the most severe glaucomatous damage classified by visual field index (VFI) was chosen for comparison. The primary outcome was blood flow rate of OA.

    Results: The mean VFI was 41% ± 26 (mean±SD) for the worse NTG eyes. The intraocular pressure was 13.6±2.6 mmHg for NTG eyes and 13.8±2.1 mmHg for control eyes. The blood flow rate in the NTG group was 9.6±3.7 ml/min compared to 11.8±5.5 ml/min in the control group. The area was 1.7±0.3 mm2 and 2.0±0.6 mm2 respectively. No statistical significance was found between NTG and the control group regarding blood flow rate (p=0.07) or OA area (p=0.12).

    Conclusions: Despite OA being an anastomosis between the intracranial and extracranial circulation, possibly generating an eye unrelated variability in blood flow, we found a trend level reduction of approximately 2 ml/min in NTG. The finding warrants blood flow rate analysis of smaller arteries specifically supplying the eye, e.g. the central retinal artery.

  • 46.
    Kristiansen, Martin
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Qvarlander, Sara
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    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). Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Ambarki, Khalid
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Hallberg, Per
    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).
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Jóhannesson, Gauti
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
    Feasibility of MRI to assess differences in ophthalmic artery blood flow rate in normal tension glaucoma and healthy controls2021In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 99, no 5, p. e679-e685Article in journal (Refereed)
    Abstract [en]

    Purpose: To examine feasibility of phase-contrast magnetic resonance imaging (PCMRI) and to assess blood flow rate in the ophthalmic artery (OA) in patients with normal tension glaucoma (NTG) compared with healthy controls.

    Methods: Sixteen patients with treated NTG and 16 age- and sex-matched healthy controls underwent PCMRI using a 3-Tesla scanner and ophthalmological examinations. OA blood flow rate was measured using a 2D PCMRI sequence with a spatial resolution of 0.35 mm(2).

    Results: The blood flow rate in the NTG group was 9.6 +/- 3.9 ml/min [mean +/- SD] compared with 11.9 +/- 4.8 ml/min in the control group. Resistance Index (RI) and Pulsatility Index (PI) were 0.73 +/- 0.08 and 1.36 +/- 0.29, respectively, in the NTG group and 0.68 +/- 0.13 and 1.22 +/- 0.40, respectively, in the healthy group. The mean visual field index (VFI) was 46% +/- 25 for the worse NTG eyes. The measured differences observed between the NTG group and the control group in blood flow rate (p = 0.12), RI (p = 0.18) and PI (p = 0.27) were non-significant.

    Conclusions: This case-control study, using PCMRI, showed a slight, but non-significant, reduction in OA blood flow rate in the NTG patients compared with the healthy controls. These results indicate that blood flow may be of importance in the pathogenesis of NTG. Considering that only a limited portion of the total OA blood flow supplies the ocular system and the large inter-individual differences, a larger study or more advanced PCMRI technique might give the answer.

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  • 47.
    Linden, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Aspects on prostanoid and cholinergic effects on aqueous humour dynamics in human eyes1999In: Acta Ophthalmologica Scandinavica, ISSN 1395-3907, E-ISSN 1600-0420, Vol. 77, no 6, p. 725-726Article in journal (Refereed)
  • 48.
    Linden, Christina
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Heijl, Anders
    Jóhannesson, Gauti
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
    Aspberg, Johan
    Andersson Geimer, Sabina
    Bengtsson, Boel
    Initial intraocular pressure reduction by mono‐ versus multi‐therapy in patients with open‐angle glaucoma: results from the Glaucoma Intensive Treatment Study2018In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 96, no 6, p. 567-572Article in journal (Refereed)
    Abstract [en]

    Purpose: To study newly diagnosed glaucoma patients given mono‐ or multi‐therapy regarding differences in initial intraocular pressure (IOP) reduction, target IOP levels reached and influence of untreated baseline IOP on IOP reduction.

    Methods: Patients newly diagnosed with manifest primary open‐angle glaucoma and included in the Glaucoma Intensive Treatment Study (GITS) were randomized to immediate intensive treatment with any of three different IOP‐lowering substances supplied in two bottles plus 360° laser trabeculoplasty or to conventional stepwise treatment starting with a single‐drug. Intraocular pressure reduction was analysed 1 month after initiation of treatment.

    Results: One hundred eighteen patients (143 eyes) received mono‐therapy and 122 patients (152 eyes) multi‐therapy. Median baseline IOP was 24.0 (min: 9.7, max: 56.0) mmHg in mono‐therapy eyes and 24.0 (min: 12.3, max: 48.5) mmHg in multi‐therapy eyes (p = 0.56). After 1 month in the two groups, respectively, values for median IOP reduction were 6.3 (range: −5.3–31.0) and 11.0 (range: 0.7–34.5) mmHg, and for mean relative decline 26.8 (range: −32.0–55.4) and 46.0 (range: 4.6–81.6) % (p = 0.000). A larger proportion of the multi‐therapy patients reached each target IOP level (p = 0.000). The higher the baseline IOP, the larger the observed pressure reduction, considering both absolute and relative figures. The effect was more pronounced in eyes with multi‐therapy than in those with mono‐therapy (p = 0.000). For every mmHg higher IOP at baseline, the IOP was reduced by an additional 0.56 (mono‐therapy) or 0.84 (multi‐therapy) mmHg.

    Conclusion: Intensive treatment led to considerably greater IOP reduction than mono‐therapy. Among patients with IOP ≥30 mmHg at diagnosis an IOP of <16 was reached in 2/3 of those with multi‐therapy but in none with mono‐therapy. The IOP reduction was highly dependent on the untreated IOP level.

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  • 49.
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Aspects on prostanoid and cholinergic effects on aqueous humour dynamics in human eyes1997Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The discovery of the ocular hypotensive effect of topically applied prostaglandins (PGs) has raised a number of questions about the mechanisms of action involved. The aim of the present thesis was to answer some of these questions.

    PGs reduce the intraocular pressure (IOP) by increasing uveoscleral flow through the ciliary muscle, but the exact mechanism is not known. Morphological changes may be involved. PGs are also involved in the inflammatory response. In the first study the aim was to investigate the effect of latanoprost, a prostaglandin F2 a-analogue, on the blood-aqueous barrier and the IOP restoration after long-term treatment. 26 glaucoma patients were treated with latanoprost (50 pg/ml) once daily for 6-12 months. Aqueous protein concentration was followed with a laser flare meter in 16 patients throughout this period. No change was observed. IOP increased slowly after withdrawal of treatment. It was concluded that latanoprost has no clinically significant effect on the permeability of the blood-aqueous barrier and that the IOP will return to pretreatment levels within a few weeks, indicating that any changes in the ciliary muscle morphology are reversible.

    In 20 healthy volunteers it was attempted to prevent the ocular hypotensive effect of latanoprost by inhibiting uveoscleral flow by a pronounced ciliary muscle contraction. For this purpose a high dose of the cholinergic agonist, physostigmine (1 drop 8 mg/ml alternate hours) was used. However, the effects on IOP of the two drugs were mainly additive most likely due to a short-lasting effect of physostigmine on the ciliary muscle.

    The progressive IOP reduction by physostigmine in the second study raised the question as to whether the drug reduces aqueous flow apart from enhancing outflow. On the contrary, in the third study repeated administrations of physostigmine, in 20 normal subjects, increased aqueous flow, measured with fluorophotometry, by about 25%.

    From studies of patients it is known that latanoprost twice daily has less ocular hypotensive effect than once daily. This was the subject of the two remaining studies. The possibility that latanoprost causes a short-lasting increase in aqueous flow was examined in 18 healthy volunteers. Application of a second drop in the morning would blunt some of the early IOP lowering effect of latanoprost. Once or twice daily applications had similar effect on aqueous flow, a tendency to an increase without any difference between the dose regimens. The next study confirmed the difference in effect on IOP between once and twice daily applications in 40 normal subjects. The difference remained even when one of the two applications was omitted after two weeks’ treatment. The results indicate that applying latanoprost twice daily induces a modest receptor desensitisation.

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  • 50.
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Therapeutic potential of prostaglandin analogues in glaucoma2001In: Expert Opinion on Investigational Drugs, ISSN 1354-3784, E-ISSN 1744-7658, Vol. 10, no 4, p. 679-694Article in journal (Refereed)
    Abstract [en]

    One of the most recent contributions to the therapeutic arsenal available for the treatment of glaucoma is the prostaglandin (PG) analogues. They represent a new class of ocular hypotensive drugs, targeting the uveoscleral outflow of ocular aqueous humour. Two drugs, latanoprost and unoprostone, are presently commercially available. In terms of intraocular pressure (IOP) reduction, latanoprost is the most powerful drug in clinical use today. The once daily dosing promotes compliance. Additional effect is achieved in combination with other hypotensive drugs, including those that increase trabecular outflow facility. The most frequent side effect is increased iris pigmentation that seems to be irreversible. A low frequency of cystoid macular oedema has been reported, predominantly in patients whose blood-retinal barrier (BRB) is compromised. Systemic side effects are rare. The experience with unoprostone is still much less than that with latanoprost. The ocular hypotensive mechanism of action of unoprostone is not well documented but an increase in uveoscleral outflow may be at least a part of its mode of action. Systemic side effects are rare and the ocular side effects seem to be mild. The ocular hypotensive effect is less than that of latanoprost and may not be suitable for monotherapy. It is widely accepted that the IOP alone is not responsible for the development of glaucomatous visual defects. It remains to be seen if this class of drugs will preserve vision in glaucoma patients better than other classes. More PG analogues are under development for potential clinical use.

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