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1.
  • Ahlm, Clas, 1956-, et al. (author)
  • Central nervous system and ophthalmic involvement in nephropathia epidemica (European type of haemorrhagic fever with renal syndrome)
  • 1998
  • In: Journal of Infection. - 0163-4453 .- 1532-2742. ; 36:2, s. 149-155
  • Journal article (peer-reviewed)abstract
    • 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.
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3.
  • Ambarki, Khalid, et al. (author)
  • Blood flow of ophthalmic artery in healthy individuals determined by phase-contrast magnetic resonance imaging
  • 2013
  • In: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 54:4, s. 2738-2745
  • Journal article (peer-reviewed)abstract
    • 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.
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4.
  • Andelid, Kristina, 1953, et al. (author)
  • Systemic cytokine signaling via IL-17 in smokers with obstructive pulmonary disease: a link to bacterial colonization?
  • 2015
  • In: International Journal of Chronic Obstructive Pulmonary Disease. - : Informa UK Limited. - 1178-2005. ; 10, s. 689-702
  • Journal article (peer-reviewed)abstract
    • We examined whether systemic cytokine signaling via interleukin (IL)-17 and growth-related oncogene-alpha (GRO-alpha) is impaired in smokers with obstructive pulmonary disease including chronic bronchitis (OPD-CB). We also examined how this systemic cytokine signaling relates to bacterial colonization in the airways of the smokers with OPD-CB. Currently smoking OPD-CB patients (n=60, corresponding to Global initiative for chronic Obstructive Lung Disease [ GOLD] stage I-IV) underwent recurrent blood and sputum sampling over 60 weeks, during stable conditions and at exacerbations. We characterized cytokine protein concentrations in blood and bacterial growth in sputum. Asymptomatic smokers (n=10) and never-smokers (n=10) were included as control groups. During stable clinical conditions, the protein concentrations of IL-17 and GRO-alpha were markedly lower among OPD-CB patients compared with never-smoker controls, whereas the asymptomatic smoker controls displayed intermediate concentrations. Notably, among OPD-CB patients, colonization by opportunistic pathogens was associated with markedly lower IL-17 and GRO-alpha, compared with colonization by common respiratory pathogens or oropharyngeal flora. During exacerbations in the OPD-CB patients, GRO-alpha and neutrophil concentrations were increased, whereas protein concentrations and messenger RNA for IL-17 were not detectable in a reproducible manner. In smokers with OPD-CB, systemic cytokine signaling via IL-17 and GRO-alpha is impaired and this alteration may be linked to colonization by opportunistic pathogens in the airways. Given the potential pathogenic and therapeutic implications, these findings deserve to be validated in new and larger patient cohorts.
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5.
  • Andelid, Kristina, 1953, et al. (author)
  • Systemic signs of neutrophil mobilization during clinically stable periods and during exacerbations in smokers with obstructive pulmonary disease
  • 2015
  • In: International Journal of Chronic Obstructive Pulmonary Disease. - : Informa UK Limited. - 1178-2005. ; 10, s. 1253-1263
  • Journal article (peer-reviewed)abstract
    • Background: It is still unclear whether signs of neutrophil mobilization in the blood of patients with chronic obstructive pulmonary disease represent true systemic events and how these relate to bacterial colonization in the airways. In this study, we evaluated these issues during clinically stable periods and during exacerbations in smokers with obstructive pulmonary disease and chronic bronchitis (OPD-CB). Methods: Over a period of 60 weeks for each subject, blood samples were repeatedly collected from 60 smokers with OPD-CB during clinically stable periods, as well as during and after exacerbations. Myeloperoxidase (MPO) and neutrophil elastase (NE) protein and mRNA, growth of bacteria in sputum, and clinical parameters were analyzed. Ten asymptomatic smokers and ten never-smokers were included as controls. Results: We found that, during clinically stable periods, neutrophil and NE protein concentrations were increased in smokers with OPD-CB and in the asymptomatic smokers when compared with never-smokers. During exacerbations, neutrophil and MPO protein concentrations were further increased in smokers with OPD-CB, without a detectable increase in the corresponding mRNA during exacerbations. However, MPO and NE protein and mRNA displayed positive correlations. During exacerbations, only increased neutrophil concentrations were associated with growth of bacteria in sputum. Among patients with low transcutaneous oxygen saturation during exacerbations, PaO2 (partial oxygen pressure) correlated with concentrations of MPO and NE protein and neutrophils in a negative manner. Conclusion: There are signs of systemic neutrophil mobilization during clinically stable periods and even more so during exacerbations in chronic obstructive pulmonary disease. In this condition, MPO and NE may share a cellular origin, but its location remains uncertain. Factors other than local bacteria, including hypoxemia, may be important for driving systemic signs of neutrophil mobilization.
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6.
  • Aspberg, Johan, et al. (author)
  • Intraocular Pressure Lowering Effect of Latanoprost as First-line Treatment for Glaucoma
  • 2018
  • In: Journal of glaucoma. - : Lippincott Williams & Wilkins. - 1057-0829 .- 1536-481X. ; 27:11, s. 976-980
  • Journal article (peer-reviewed)abstract
    • 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.
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7.
  • Aström, Siv, et al. (author)
  • Incidence and prevalence of pseudoexfoliation and open-angle glaucoma in northern Sweden : I. Baseline report.
  • 2007
  • In: Acta Ophthalmologica Scandinavica. - : Wiley. - 1395-3907 .- 1600-0420. ; 85:8, s. 828-831
  • Journal article (peer-reviewed)abstract
    • 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%.
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8.
  • Beckman Rehnman, Jeannette, et al. (author)
  • Increased corneal hysteresis after corneal collagen crosslinking : a study based on applanation resonance technology
  • 2014
  • In: JAMA ophthalmology. - : American Medical Association. - 2168-6165 .- 2168-6173. ; 132:12, s. 1426-1432
  • Journal article (peer-reviewed)abstract
    • 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.
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9.
  • Beckman Rehnman, Jeannette, et al. (author)
  • Initial results from mechanical compression of the cornea during crosslinking for keratoconus
  • 2014
  • In: Acta Ophthalmologica. - : John Wiley & Sons. - 1755-375X .- 1755-3768. ; 92:7, s. 644-649
  • Journal article (peer-reviewed)abstract
    • 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.
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10.
  • Beckman Rehnman, Jeannette, 1969- (author)
  • New methods to evaluate the effect of conventional and modified crosslinking treatment for keratoconus
  • 2015
  • Doctoral thesis (other academic/artistic)abstract
    • Background: Today corneal crosslinking with ultraviolet-A photoactivation of riboflavin is an established method to halt the progression of keratoconus. In some cases, when the refractive errors are large and the visual acuity is low, conventional corneal crosslinking may not be sufficient. In these cases it would be desirable with a treatment that both halts the progression and also reduces the refractive errors and improves the quality of vision.Aims:  The aims of this thesis were to determine whether mechanical compression of the cornea during corneal crosslinking for keratoconus using a sutured rigid contact lens could improve the optical and visual outcomes of the treatment, and also to find methods to evaluate the effect of different corneal crosslinking treatment regimens.Methods: In a prospective, open, randomized case-control study, 60 eyes of 43 patients with progressive keratoconus, aged 18-28 years, planned for routine corneal crosslinking, and a corresponding age- and sex-matched control group was included. The patients were randomized to conventional corneal crosslinking (CXL; n=30) or corneal crosslinking with mechanical compression of the cornea during the treatment (CRXL; n=30).Biomicroscopy, autorefractometry, best spectacle corrected visual acuity, axial length measurement, Pentacam® HR Scheimpflug photography, pachymetry, intraocular pressure measurements and corneal biomechanical assessments were performed before treatment (baseline) and at 1 month and 6 months after the treatment.One of the articles evaluated and compared the optical and visual outcomes between CXL and CRXL, while the other three articles focused on methods to evaluate treatment effects. In Paper I, the corneal light scattering was manually quantified from Scheimpflug images throughout the corneal thickness at 8 measurements points, 0.0 to 3.0 mm from the corneal centre, in patients treated with CXL. In Paper IV the corneal densitometry (light scattering) was measured with the Pentacam® HR software, in 4 circular zones around the corneal apex and at 3 different depths of the corneal stroma, in both CXL and CRXL treated corneas. Paper III quantified the biomechanical effects of CXL in vivo.Results: Corneal light scattering after CXL showed distinctive spatial and temporal profiles and Applanation Resonance Tonometry (ART) -technology demonstrated an increased corneal hysteresis 1 and 6 months after CXL. When comparing the refractive and structural results after CXL and CRXL, CRXL failed to flatten the cornea, and the treatment did not show any benefits to conventional CXL treatment, some variables even indicated an inferior effect. Accordingly, the increase in corneal densitometry was also less pronounced after CRXL.Conclusions: Analysis of corneal light scattering/densitometry shows tissue changes at the expected treatment location, and may be a relevant variable in evaluating the crosslinking effect. ART -technology is an in vivo method with the potential to assess the increased corneal hysteresis after CXL treatment. By refining the method, ARTmay become a useful tool in the future. Unfortunately, CRXL does not improve the optical and visual outcomes after corneal crosslinking. Possibly, stronger crosslinking would be necessary to stabilize the cornea in a flattened position.
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11.
  • Beckman Rehnman, Jeannette, et al. (author)
  • Spatial distribution of corneal light scattering after corneal collagen crosslinking
  • 2011
  • In: Journal of cataract and refractive surgery. - Fairfax,Va. : American Society of Cataract and Refractive Surgery. - 0886-3350 .- 1873-4502. ; 37:11, s. 1939-1944
  • Journal article (peer-reviewed)abstract
    • 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.
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12.
  • Beckman Rehnman, Jeannette, et al. (author)
  • Treatment Effect and Corneal Light Scattering With 2 Corneal Cross-linking Protocols : A Randomized Clinical Trial
  • 2015
  • In: JAMA ophthalmology. - : American Medical Association (AMA). - 2168-6165 .- 2168-6173. ; 133:11, s. 1254-1260
  • Journal article (peer-reviewed)abstract
    • 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.
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13.
  • Beecham, Ashley H, et al. (author)
  • Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis.
  • 2013
  • In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:11, s. 1353-60
  • Journal article (peer-reviewed)abstract
    • Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10(-4)). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 × 10(-8)), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.
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14.
  • Behndig, Anders, et al. (author)
  • Aqueous humor lidocaine concentrations in topical and intracameral anesthesia
  • 1998
  • In: Journal of cataract and refractive surgery. - 0886-3350 .- 1873-4502. ; 24:12, s. 1546-1647
  • Journal article (peer-reviewed)abstract
    • 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.
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15.
  • Bengtsson, Boel, et al. (author)
  • The glaucoma intensive treatment study : interim results from an ongoing longitudinal randomized clinical trial
  • 2022
  • In: Acta Ophthalmologica. - : John Wiley & Sons. - 1755-375X .- 1755-3768. ; 100:2, s. e455-e462
  • Journal article (peer-reviewed)abstract
    • 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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16.
  • Bengtsson, Boel, et al. (author)
  • The glaucoma intensive treatment study (GITS) : a randomized controlled trial comparing intensive and standard treatment on 5 years visual field development
  • 2024
  • In: American Journal of Ophthalmology. - : Elsevier. - 0002-9394 .- 1879-1891. ; 266, s. 274-288
  • Journal article (peer-reviewed)abstract
    • PURPOSE: To assess the effect of an intensive initial intraocular pressure (IOP)–lowering treatment strategy on the progression of visual field damage. DESIGN: A randomized, controlled, open-label, 2-center clinical trial.METHODS: A total of 242 patients with newly detected early or moderate untreated open-angle glaucoma were enrolled at 2 university hospitals in Sweden. Participants were randomly allocated (1:1) to either initial treatment with intensive IOP-lowering medications followed by 360° laser trabeculoplasty (LTP), or to traditional mono-therapy, which was increased when deemed necessary. The primary study outcome of interest was the predicted remaining visual field, as measured by the visual field index (VFI) at projected end of life.RESULTS: The median untreated IOP was 24 mm Hg in both treatment groups. During follow-up, median and mode IOP were 17 mm Hg in the mono- and 14 mm Hg in the multi-treatment group. In the mono-treatment group, the median VFI at projected end of life was 79.3% and in the multi-treatment group 87.1% (P =.15). The annual rate of progression of visual field damage was faster in mono-treatment than in multi-treatment participants; median losses per year were 0.65 and 0.25 percentage units, respectively (P =.09). Progression events occurred in 21% of the mono- and in 11% of the multi-treatment participants (P =.03). Adverse events, mostly mild, were reported in 25% of the mono- and in 36% of the multi-treatment participants. Differences in visual field outcomes between treatment groups were more pronounced in participants having higher baseline IOP, defined by median split of untreated IOP values.CONCLUSIONS: In the overall analysis, the visual field outcomes were not overwhelmingly better in the multi-treatment group, but post hoc analysis showed definite benefit in patients with higher untreated IOP. Based on the results of this study, initial intensive treatment may be considered in glaucoma patients with high untreated IOP at diagnosis, although we found no evidence that multi-therapy should be given routinely to all glaucoma patients.
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17.
  • Bengtsson, Boel, et al. (author)
  • The Glaucoma Intensive Treatment Study (GITS), a randomized clinical trial : design, methodology and baseline data
  • 2018
  • In: Acta Ophthalmologica. - : John Wiley & Sons. - 1755-375X .- 1755-3768. ; 96:6, s. 557-566
  • Journal article (peer-reviewed)abstract
    • 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.
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18.
  • Bergstrand, Sara, et al. (author)
  • Blood flow measurements at different depths using photoplethysmography and laser Doppler techniques
  • 2009
  • In: Skin research and technology. - : Wiley-Blackwell. - 0909-752X .- 1600-0846. ; 15:2, s. 139-147
  • Journal article (peer-reviewed)abstract
    • Background/purpose: This study has evaluated a multi-parametric system combining laser Doppler flowmetry and photoplethysmography in a single probe for the simultaneous measurement of blood flow at different depths in the tissue. This system will be used to facilitate the understanding of pressure ulcer formation and in the evaluation of pressure ulcer mattresses.Methods: The blood flow in the tissue over the sacrum was measured before, during and after loading with 37.5 mmHg, respectively, 50.0 mmHg. The evaluation of the system consisted of one clinical part, and the other part focusing on the technicalities of the probe prototype.Results: An increase in blood flow while loading was the most common response, but when the blood flow decreased during loading it was most affected at the skin surface and the blood flow responses may be different due to depths of measurement. Reactive hyperaemia may occur more frequently in the superficial layers of the tissue.Conclusion: The study showed that the new system is satisfactory for measuring tissue blood flow at different depths. The laser Doppler complements the photoplethysmography, and further development of the system into a thin flexible probe with the ability to measure a larger area is required.
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19.
  • Bergstrand, Sara, et al. (author)
  • Existence of Tissue Blood Flow in Response to External Pressure in the Sacral Region of Elderly Individuals - Using an Optical Probe Prototype
  • 2010
  • In: MICROCIRCULATION. - : Taylor and Francis. - 1073-9688 .- 1549-8719. ; 17:4, s. 311-319
  • Journal article (peer-reviewed)abstract
    • Pandgt;Objective: The aim was to investigate the existence of sacral tissue blood flow at different depths in response to external pressure and compression in elderly individuals using a newly developed optical probe prototype. Methods: The tissue blood flow and tissue thickness in the sacral area were measured during load in 17 individuals using laser Doppler flowmetry and photoplethysmography in a combined probe, and digital ultrasound. Results: The mean age was 68.6 +/- 7.0 years. While loading, the mean compression was 60.3 +/- 11.9%. The number of participants with existing blood flow while loading increased with increased measurement depth. None had enclosed blood flow deep in the tissue and at the same time an existing more superficial blood flow. Correlation between tissue thickness and BMI in unloaded and loaded sacral tissue was shown: r = 0.68 (P = 0.003) and r = 0.68 (P = 0.003). Conclusions: Sacral tissue is highly compressed by external load. There seems to be a difference in responses to load in the different tissue layers, as occluded blood flow in deeper tissue layers do not occur unless the blood flow in the superficial tissue layers is occluded.
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20.
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21.
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22.
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23.
  • Bro, Tomas, et al. (author)
  • The future is old : patients with topical ocular hypotensive treatment in the Nordic region between 2008 and 2017 with projections for 2040
  • 2021
  • In: Acta Ophthalmologica. - : John Wiley & Sons. - 1755-375X .- 1755-3768. ; 99:2, s. e1442-e1448
  • Journal article (peer-reviewed)abstract
    • 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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24.
  • Bro, Tomas, et al. (author)
  • The More, the Better? : The Usefulness of Brimonidine as the Fourth Antiglaucoma Eye Drop
  • 2018
  • In: Journal of glaucoma. - : Wolters Kluwer. - 1057-0829 .- 1536-481X. ; 27:7, s. 643-646
  • Journal article (peer-reviewed)abstract
    • 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.
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25.
  • Byström, Berit, et al. (author)
  • Laminins in normal, keratoconus, bullous keratopathy and scarred human corneas
  • 2007
  • In: Histochemistry and Cell Biology. - : Springer Science and Business Media LLC. - 0948-6143 .- 1432-119X. ; 127:6, s. 657-667
  • Journal article (peer-reviewed)abstract
    • 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.
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26.
  • Eklund, Anders, et al. (author)
  • An applanation resonator sensor for measuring intraocular pressure using combined continuous force and area measurement
  • 2003
  • In: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 44:7, s. 3017-24
  • Journal article (peer-reviewed)abstract
    • PURPOSE: For diagnostic purposes and for follow-up after treatment, it is important to have simple and reliable methods for measuring intraocular pressure (IOP). The purpose of this study was to develop a new applanation method for IOP measurement that uses combined continuous force and area measurement and to develop and evaluate an applanation resonator sensor (ARS) tonometer based on that method. METHODS: The tonometer was developed and evaluated in an in vitro porcine eye model, in which enucleated eyes were pressurized with a saline column. A model assuming that the applanation principle is valid over a certain interval of contact area was proposed. Continuous contact area was measured with a resonator sensor device, and contact force was measured with a force transducer, both mounted together in one probe. Reference IOP was measured in the vitreous chamber (IOP(VC)) with a standard fluid pressure transducer. RESULTS: An optimization algorithm determined the applanation interval that was optimal for calculating IOP(ARS). The corresponding time interval was 30 +/- 3 to 77 +/- 4 ms (mean +/- SD, n = 418) after initial contact. The proposed model showed a degree of explanation of R(2 [supi]) = 0.991 (n = 410, six eyes), corresponding to a correlation of r = 0.995 (n = 410) between IOP(ARS) and IOP(VC). The within-eyes precision (i.e., 95% confidence interval for the residuals between IOP(ARS) and IOP(VC)) was +/- 1.8 mm Hg (n = 410, six eyes). CONCLUSIONS: In this study, the ARS method for measuring IOP was evaluated in an in vitro porcine eye model and showed high precision. The ARS method is, to the authors' knowledge, the first to combine simultaneous, continuous sampling of both parameters included in the applanation principle: force and area. Consequently, there is a potential for reducing errors in clinical IOP tonometry.
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27.
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28.
  • Eklund, Anders, et al. (author)
  • Evaluation of applanation resonator sensors for intra-ocular pressure measurement : results from clinical and in vitro studies.
  • 2003
  • In: Medical and Biological Engineering and Computing. - 0140-0118 .- 1741-0444. ; 41:2, s. 190-197
  • Journal article (peer-reviewed)abstract
    • Glaucoma is an eye disease that, in its most common form, is characterised by high intra-ocular pressure (IOP), reduced visual field and optic nerve damage. For diagnostic purposes and for follow-up after treatment, it is important to have simple and reliable methods for measuring IOP. Recently, an applanation resonator sensor (ARS) for measuring IOP was introduced and evaluated using an in vitro pig-eye model. In the present study, the first clinical evaluation of the same probe has been carried out, with experiments in vivo on human eyes. There was a low but significant correlation between IOP(ARS) and the IOP measured with a Goldmann applanation tonometer (r = 0.40, p = 0.001, n = 72). However, off-centre positioning of the sensor against the cornea caused a non-negligible source of error. The sensor probe was redesigned to have a spherical, instead of flat, contact surface against the eye and was evaluated in the in vitro model. The new probe showed reduced sensitivity to off-centre positioning, with a decrease in relative deviation from 89% to 11% (1 mm radius). For normalised data, linear regression between IOP(ARS) and direct IOP measurement in the vitreous chamber showed a correlation of r = 0.97 (p < 0.001, n = 108) and a standard deviation for the residuals of SD < or = 2.18 mm Hg (n = 108). It was concluded that a spherical contact surface should be preferred and that further development towards a clinical instrument should focus on probe design and signal analysis.
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29.
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30.
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31.
  • Grankvist, Anna, et al. (author)
  • Multi-locus sequence analysis (MLSA) of clinical "CandidatusNeoehrlichia mikurensis" strains from Europe.
  • 2015
  • In: Journal of Clinical Microbiology. - 1098-660X. ; 53:10, s. 3126-3132
  • Journal article (peer-reviewed)abstract
    • CandidatusNeoehrlichia mikurensis is the tick-borne agent of neoehrlichiosis, an infectious disease that primarily affects immunocompromised patients. So far, the genetic variability of Neoehrlichia has been studied only by comparing 16S rRNA gene and groEL operon sequences. We describe the development and use of a multi-locus sequence analysis (MLSA) protocol to characterize the genetic diversity of clinicalNeoehrlichiastrains in Europe and their relatedness to other species within the Anaplasmataceae family.Six genes were selected:ftsZ, clpB, gatB,lipA,groEL and 16SrRNA. Each MLSA locus was amplified by real-time PCR, and the PCR-products sequenced. Phylogenetic trees of MLSA locus relatedness were constructed from aligned sequences. Blood samples from 12 patients with confirmed Neoehrlichia infection from Sweden (n = 9), the Czech Republic (n = 2) and Germany (n = 1) were analyzed with the MLSA protocol.Threeof the Swedish strains exhibited identical lipA sequences, while the lipA sequences of the strains from the other nine patients were identical to each other.One of the Czech strains had one differing nucleotide in the clpB sequence from the sequences of the other 11 strains. All 12 strains had identical sequences for the genes 16SrRNA,ftsZ, gatB, and groEL.According to the MLSA, Neoehrlichia is most closely related to E. ruminantium, less so to A. phagocytophilum and least to Wolbachiaendosymbiont, among the Anaplasmataceae.To conclude, three sequence types of infectious Neoehrlichia wereidentified: one in the west of Sweden, one in the Czech Republic, and one spread throughout Europe.
  •  
32.
  • Grankvist, Anna, et al. (author)
  • Multilocus sequence analysis of clinical "candidatus neoehrlichia mikurensis" strains from Europe
  • 2015
  • In: Journal of Clinical Microbiology. - 0095-1137 .- 1098-660X. ; 53:10, s. 3126-3132
  • Journal article (peer-reviewed)abstract
    • Copyright © 2015, American Society for Microbiology. All Rights Reserved. Candidatus Neoehrlichia mikurensis" is the tick-borne agent of neoehrlichiosis, an infectious disease that primarily affects immunocompromised patients. So far, the genetic variability of "Ca. Neoehrlichia" has been studied only by comparing 16S rRNA genes and groEL operon sequences. We describe the development and use of a multilocus sequence analysis (MLSA) protocol to characterize the genetic diversity of clinical "Ca. Neoehrlichia" strains in Europe and their relatedness to other species within the Anaplasmataceae family. Six genes were selected: ftsZ, clpB, gatB, lipA, groEL, and 16S rRNA. Each MLSA locus was amplified by real-time PCR, and the PCR products were sequenced. Phylogenetic trees of MLSA locus relatedness were constructed from aligned sequences. Blood samples from 12 patients with confirmed "Ca. Neoehrlichia" infection from Sweden (n9), the Czech Republic (n2), and Germany (n1) were analyzed with the MLSA protocol. Three of the Swedish strains exhibited identical lipA sequences, while the lipA sequences of the strains from the other nine patients were identical to each other. One of the Czech strains had one differing nucleotide in the clpB sequence from the sequences of the other 11 strains. All 12 strains had identical sequences for the genes 16S rRNA, ftsZ, gatB, and groEL. According to the MLSA, among the Anaplasmataceae, "Ca. Neoehrlichia" is most closely related to Ehrlichia ruminantium, less so to Anaplasma phagocytophilum, and least to Wolbachia endosymbionts. To conclude, three sequence types of infectious "Ca. Neoehrlichia" were identified: one in the west of Sweden, one in the Czech Republic, and one spread throughout Europe.
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33.
  • Gustavsson, Simon T., et al. (author)
  • Nicotinamide prevents retinal vascular dropout in a rat model of ocular hypertension and supports ocular blood supply in glaucoma patients
  • 2023
  • In: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 64
  • Journal article (peer-reviewed)abstract
    • 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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34.
  • Hagblad, Jimmie, et al. (author)
  • A technique based on laser Doppler flowmetry and photoplethysmography for simultaneously monitoring blood flow at different tissue depths
  • 2010
  • In: Medical and Biological Engineering and Computing. - : Springer Science Business Media. - 0140-0118 .- 1741-0444. ; 48:5, s. 415-422
  • Journal article (peer-reviewed)abstract
    • The aim of this study was to validate a non-invasive optical probe for simultaneous blood flow measurement at different vascular depths combining three photoplethysmography (PPG) channels and laser Doppler flowmeter (LDF). Wavelengths of the PPG were near-infrared 810 nm with source-to-detector separation of 10 and 25 mm, and green 560 nm with source-to-detector separation of 4 mm. The probe is intended for clinical studies of pressure ulcer aetiology. The probe was placed over the trapezius muscle, and depths from the skin to the trapezius muscle were measured using ultrasound and varied between 3.8 and 23 mm in the 11 subjects included. A provocation procedure inducing a local enhancement of blood flow in the trapezius muscle was used. Blood flows at rest and post-exercise were compared. It can be concluded that this probe is useful as a tool for discriminating between blood flows at different vascular tissue depths. The vascular depths reached for the different channels in this study were at least 23 mm for the near-infrared PPG channel (source-to-detector separation 25 mm), 10-15 mm for the near-infrared PPG channel (separation 10 mm), and shallower than 4 mm for both the green PPG channel (separation 4 mm) and LDF.
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35.
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36.
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37.
  • Hallberg, Per, et al. (author)
  • Applanation resonance tonometry for intraocular pressure in humans
  • 2004
  • In: Physiological Measurement. - : IOP Publishing. - 0967-3334 .- 1361-6579. ; 25:4, s. 1053-1065
  • Journal article (peer-reviewed)abstract
    • 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.
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38.
  • Hallberg, Per, 1965- (author)
  • Applanation Resonance Tonometry for Intraocular Pressure Measurement
  • 2006
  • Doctoral thesis (other academic/artistic)abstract
    • Elevated intraocular pressure (IOP) is one of the major risk factors for glaucoma. Since glaucoma is a leading cause of blindness, reliable methods for measuring the IOP are important. This doctoral dissertation presents a new method, applanation resonance tonometry (ART), for measurement of IOP. The method is based on resonance sensor technology combined with the novel multipoint analysis of continuously sampled data of both contact force and contact area. The ART was evaluated in in vitro porcine-eye studies as well as in clinic on both healthy volunteers and patients. A new symmetric probe with a larger sensor tip and improved aligning light was developed and evaluated in vitro. It showed that the error from off-centring was highly reduced. The new ART probe, used as a biomicroscope device (ARTBiom) and as a handheld device (ARTHand), was further evaluated in a clinical study designed in accordance with the International Standard Organisation’s (ISO) requirement. Both the ARTBiom and the ARTHand met the precision set by the requirements. Laser surgery is a common way to correct vision. The biomechanical effect of photorefractive keratectomy (PRK) on IOP measurements was evaluated using Goldmann applanation tonometry (GAT) and ART in an in vitro study. Both methods were affected, but to a different extent. The flat contact probe of GAT, as compared with the convex tip of ART, and single point vs. multipoint approach, provide explanation to the ART advantage regarding measurement error of IOP after PRK. In conclusion, resonance sensor technology has made it possible to introduce a new multipoint method for measuring IOP, and the method is relevant for measuring IOP in humans. It may be possible to reduce errors in the clinical measurement of IOP with this new method, especially after corneal surgery. The ART has the potential to become a useful clinical instrument for IOP measurement.
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39.
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40.
  • Hallberg, Per, et al. (author)
  • Clinical evaluation of applanation resonance tonometry : a comparison with Goldmann applanation tonometry.
  • 2007
  • In: Journal of glaucoma. - : Ovid Technologies (Wolters Kluwer Health). - 1057-0829 .- 1536-481X. ; 16:1, s. 88-93
  • Journal article (peer-reviewed)abstract
    • 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.
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41.
  • Hallberg, Per, et al. (author)
  • Comparison of Goldmann applanation and applanation resonance tonometry in a biomicroscope-based in vitro porcine eye model
  • 2006
  • In: Journal of Medical Engineering & Technology. - : Informa UK Limited. - 0309-1902 .- 1464-522X. ; 30:6, s. 345-52
  • Journal article (peer-reviewed)abstract
    • We have developed an in vitro porcine eye model based on a biomicroscope, to simulate a clinical situation for IOP measurement on enucleated eyes. The aims of this study were to evaluate the model and to apply and compare Goldmann applanation tonometry (GAT) and applanation resonance tonometry (ART) measurements in porcine eyes. The GAT measurement (IOPGAT) showed a lower pressure, mean - 14.0 mm Hg (SD = 1.7 mm Hg) as compared with the reference pressure. For in vitro measurement with GAT on porcine eyes the linear calibration was IOP = 1.14 IOPGAT + 12.5 mm Hg (R2 = 0.99, p < 0.001, n = 280, four eyes). ART measurements correlated significantly to reference IOP, R = 0.86 (p < 0.001, n = 252, six eyes), with a mean difference of 5.4 mm Hg (SD = 6.7 mm Hg). GAT could only be used on porcine eyes if the IOP exceeded 13 mm Hg. Evaluation of the ART in this in vitro model showed position dependence for the sensor. To facilitate centre positioning a guiding tool is suggested. Porcine eyes are a possible substitute for human eyes in in vitro models for pre-clinical evaluation of new tonometry methods.
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42.
  • Hallberg, Per, et al. (author)
  • Symmetric sensor for applanation resonance tonometry of the eye
  • 2006
  • In: Medical and Biological Engineering and Computing. - : Springer Science and Business Media LLC. - 0140-0118 .- 1741-0444. ; 44:1-2, s. 54-60
  • Journal article (peer-reviewed)abstract
    • 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.
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43.
  • Hallberg, Per, et al. (author)
  • Underestimation of intraocular pressure after photorefractive keratectomy : a biomechanical analysis
  • 2006
  • In: Medical and Biological Engineering and Computing. - : Springer. - 0140-0118 .- 1741-0444. ; 44, s. 609-618
  • Journal article (peer-reviewed)abstract
    • 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.
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44.
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45.
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46.
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47.
  • Heijl, Anders, et al. (author)
  • Öppenvinkelglaukom: diagnostik, uppföljning och behandling : En systematisk litteraturöversikt från SBU
  • 2010
  • In: Läkartidningen. - 0023-7205 .- 1652-7518. ; 107:19-20, s. 1311-1313
  • Journal article (peer-reviewed)abstract
    • 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.
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48.
  • Johannesson, Gauti, et al. (author)
  • Age-dependency of ocular parameters : a cross sectional study of young and elderly healthy subjects
  • 2015
  • In: Graefe's Archives for Clinical and Experimental Ophthalmology. - : Springer. - 0721-832X .- 1435-702X. ; 253:11, s. 1979-1983
  • Journal article (peer-reviewed)abstract
    • 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.
  •  
49.
  • Johannesson, Gauti, et al. (author)
  • Age-dependency of ocular parameters - a cross sectional study of young and old healthy subjects
  • 2015
  • In: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology. - 0146-0404 .- 1552-5783. ; 56:7
  • Journal article (other academic/artistic)abstract
    • 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.
  •  
50.
  • Jóhannesson, Gauti, 1979-, et al. (author)
  • Can the prevalence of open-angle glaucoma be estimated from a retrospective clinical material? A study on the west coast of Iceland.
  • 2005
  • In: Acta Ophthalmologica Scandinavica. - : Wiley. - 1395-3907 .- 1600-0420. ; 83:5, s. 549-553
  • Journal article (peer-reviewed)abstract
    • 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.
  •  
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