| 1. |
- Baptista, Antonio M. G., et al.
(författare)
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Causes of Vision Impairment in Portugal : A hospital based study
- 2015
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Ingår i: Investigative Ophthalmology and Visual Science. - 0146-0404 .- 1552-5783. ; 56:7
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Causes of vision impairment (VI) are influenced by factors such as race or socio-economic circumstances. Because of this collecting national information is important for planning reduction of vision loss. The aim of this study was to determine causes of vision impairment in a population visiting ophthalmology departments in public hospitals in Portugal.Methods This study was designed according with the guidelines of the Vancouver Economic Burden of Vision Loss Group (IOVS, 2010, V51/4/1801). Recommendations are to collect hospital data during 1 year to determine causes of VI. We selected four public hospitals that are expected to have over 120-140K appointments per year. Files are analysed weekly to detect patients with vision impairment. Inclusion criteria are: visual acuity with the current refractive correction equal or less than 0.5 (20/40) in the better-seeing eye and/or a visual field of less than 20 degrees. Patients were selected by trained hospital staff (medics and orthoptists) and inserted in a database. Diagnoses were classified according the ICD9. Data collected included fundamental demographic information, main diagnosis, secondary diagnosis and comorbidities.Results We have now 2462 patients selected that correspond to 4 to 33 weeks of data collection. The number of weeks is variable because we did not start all hospitals simultaneously. From the current number of cases detected, 58% are female, 1.9% are under 20, 8.2% are between 20 and 50 and 89.9% are 50 years or older. The leading causes of vision impairment among these patients are diabetic retinopathy (DR), cataract (C), glaucoma (GC) and age-related macular degeneration (AMD). Using the North American definition of VI the proportions are 26.8% for DR, 25.5% for C, 10.4% for GC and 8.2% for AMD. The remaining causes of VI have percentages below 5% and in total they correspond to approximately 29% of the cases detected.Conclusions Our results show that the most common causes of vision impairment are eye diseases related with systemic conditions and aging of the population. Vision impairment was relatively low under the age of 20 and the causes were mostly inherited diseases. Numbers reported now will be more accurate at the end of the study but they already highlight the importance of targeting conditions such as diabetes.
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| 2. |
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| 3. |
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| 4. |
- Bengtsson, Boel, et al.
(författare)
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Lack of visual field improvement after initiation of intraocular pressure reducing treatment in the early manifest glaucoma trial
- 2016
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404. ; 57:13, s. 5611-5615
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. We evaluate how visual fields are affected by the initiation of IOP-reducing therapy in previously untreated glaucoma individuals. METHODS. Qualifying individuals with newly diagnosed glaucoma having normal to moderately elevated IOP were prospectively randomized either to IOP-reducing therapy or to no treatment. Before randomization, individuals underwent repeatedly Standard Automated Perimetry (SAP) testing and Goldmann tonometry. Three months after randomization, patients again underwent SAP and tonometry. Changes between baseline and the 3-month follow-up visit in the perimetric summary index, mean deviation (MD), and total deviation values at significantly depressed test points were compared between the treated and untreated groups. RESULTS. Of 255 individuals studied, 129 were randomized to treatment and 126 to no treatment. Intraocular pressure decreased by an average of 24% among treated and by 0.6% in the untreated patients. Mean deviation deteriorated slightly in both groups; mean change was-0.15 and-0.44 dB in the treated and untreated groups, respectively; the difference was not statistically significant, (P = 0.16). No association was seen between IOP reduction and change in MD. Sensitivities decreased slightly in significantly depressed test points, mean change was-0.45 dB in the untreated and-0.38 dB in the treated groups (P = 0.88). CONCLUSIONS. Observed visual field changes among glaucoma patients receiving initial IOPreducing therapy were not significantly different to changes seen in patients who received no treatment. Thus, our results did not support the idea that visual field status improves after initiation of IOP-reducing therapy in glaucoma individuals, at least not in individuals with initially normal to moderately elevated IOPs.
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| 5. |
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| 6. |
- Borbely, Gabor, 1981-, et al.
(författare)
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The role of neurokinin A in corneal wound repair
- 2015
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Ingår i: Investigative Ophthalmology and Visual Science. - Rockville, MD, USA : Assoc Research Vision Ophthalmology Inc. - 0146-0404 .- 1552-5783. ; 56:7
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 7. |
- Burstedt, Marie, et al.
(författare)
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Phenotypic expression of EYS mutations in patients with autosomal recessive retinitis pigmentosa in northern Sweden
- 2018
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Ingår i: Investigative Ophthalmology and Visual Science. - : The Association for Research in Vision and Ophthalmology, Inc.. - 0146-0404 .- 1552-5783. ; 59:9
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Purpose : To describe clinical phenotype in patients of northern Sweden affected by recessive retinitis pigmentosa (ARRP) caused by mutations in Eyes Shut Homolog (Drosophila) (EYS) gene.Methods : Whole exome sequencing (WES) and multiple ligation dependent prode amplification (MLPA) were used for identification of EYS sequence variants in a cohort of ARRP patients (n=148) from northern Sweden. The patients with EYS mutations were ophthalmologically examined over time using visual acuity (ETDRS), visual fields, slit lamp and fundus examination and ocular coherence tomography (OCT). Dark adaptometry and full-field electroretionograms (ERG) was performed.Results : Phenotype characterization was done in 13 ARRP cases with EYS mutations representing five bi-allelic sequence variants, three of which were novel. Only one variant was detected in two cases. The phenotypic outcome was predominately presented as classical RP aggravating in young adulthood. However, among these patients we observed a variation of phenotypic expression with initial paracentral to central macular affection of the retina and areolar retinal degeneration with electrophysiological outcome of only slightly subnormal responses of both rods and cones in late adulthood (60 y/o), clinically defined as areolar atrophy.Conclusions : The EYS mutations account for 10% of ARRP in northern Sweden. The phenotype presents both typical classical RP and chorioretinal degenerative retinal disease, areolar dystrophy. This suggests that molecular genetic testing of the EYS is crucial when both RP and pattern macular diseases are clinically diagnosed.
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| 8. |
- Byström, Berit, et al.
(författare)
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Notch1 Signaling Pathway in Aniridia- Related Keratopathy, Normal Fetal and Adult Human Corneas
- 2018
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Ingår i: Investigative Ophthalmology and Visual Science. - : The Association for Research in Vision and Ophthalmology, Inc.. - 0146-0404 .- 1552-5783. ; 59:9
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Purpose : Notch1 is suggested to play an important role during tissue development and in differentiation of the corneal epithelial cells whereas its inhibitors Dlk1 and Numb keep these cells in an immature status. Our purpose was to evaluate the presence of these factors in aniridia-related keratopathy (ARK) and in normal fetal and adult human corneas.Methods : Two human fetal corneas, 10 and 20 weeks of gestation, two naïve corneal buttons from patients with advanced ARK, three corneal buttons from patients with ARK undergoing re-transplantation, as well as two adult healthy control corneas were processed for immunohistochemistry using antibodies against Notch1, Dlk1 and Numb.Results : Identical staining patterns were found for Notch1 in normal adult and fetal corneas, with staining around the basal epithelial cells and in a few streaks in the stroma. In ARK corneas, Notch1 was not detected in the pannus of the stroma. On the contrary, the pannus in ARK was labeled with antibodies against Dlk1. Dlk1 was also abundant in the epithelium and in the stroma of fetal corneas but was absent from the stroma of normal adult corneas. Numb was present in the adult normal corneas and in addition labeled the ARK and fetal corneas in a pattern resembling that of Dlk1.Conclusions : The lack of Notch1 together with abundant Dlk1 and Numb, suggest a disturbed balance between these important factors in ARK, likely to hamper differentiation of the progenitor cell population and to be important for the pathophysiology of ARK.
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| 9. |
- Carneiro de Freitas, Rui, et al.
(författare)
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Prevalence of Visual Impairment in Portugal : study design and initial results
- 2015
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Ingår i: Investigative Ophthalmology and Visual Science. - 0146-0404 .- 1552-5783. ; 56:7
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Information about the prevalence of visual impairment is fundamental to define policies that deal with vision loss. The aim of this study is to determine the prevalence of visual impairment (VI) in the population looking for eye care in public hospitals in Portugal.Methods We designed an observation, cross-sectional prospective study (Prevalence and Costs of Visual Impairment in Portugal: PC-VIP study) to investigate the prevalence of VI in patients attending outpatient appointments in four public hospitals in Portugal. Hospital selected provide from general eye care (3-6 ophthalmologists) to high-specialized eye care (40+ ophthalmologists) that in total have between 120-140K hospital appointments per year. Files of patients are analysed weekly to detect patients with VI. Inclusion criteria were: visual acuity equal or worse than 0.5 (USA definition 20/40) in the better eye and/or a visual field of less than 20deg. Cases are selected by trained hospital staff and inserted in a database. Data collected included demographic information, acuity from both eyes, qualitative information about visual field (good, reduced, requires investigation), main diagnosis, secondary diagnosis and comorbidities. Diagnoses were classified according with ICD9.Results We have now detected 2462 cases of VI that correspond to 4 to 33 weeks of data collection. The number of weeks is variable because collection did not start simultaneously in all sites. From the number of cases detected, 58% were female, 1.9% were under 20y, 8.2% were between 20y and 50y and 89.9% were ≥50y. The mean prevalence of visual impairment was 13.6% (SD=5.6) using the USA definition and it was 7.0%(SD=4.1) using the WHO definition (acuity equal or worse than 0.3 or ~20/63). With a methodology that controls for demographics the lowest and highest estimates were calculated. Considering the USA definition, the prevalence in the general population would be in the range 0.4 -0.4% (age<40y) and 0.8-2.4% (age>=40y). Considering WHO definition, it would be 0.2-0.5% (age<40y) and 0.4-1.0% (age>=40y).Conclusions A hospital-based study can provide effective estimates of the prevalence of visual impairment in a population. Estimates for the country are in agreement with the expected results that can be deducted from neighbour countries and self-reported visual impairment in census 2001.
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| 10. |
- Chen, Wei Sheng, et al.
(författare)
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Galectin-3 inhibition by a small-molecule inhibitor reduces both pathological corneal neovascularization and fibrosis
- 2017
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404. ; 58:1, s. 9-20
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. Corneal neovascularization and scarring commonly lead to significant vision loss. This study was designed to determine whether a small-molecule inhibitor of galectin-3 can inhibit both corneal angiogenesis and fibrosis in experimental mouse models. METHODS. Animal models of silver nitrate cautery and alkaline burn were used to induce mouse corneal angiogenesis and fibrosis, respectively. Corneas were treated with the galectin-3 inhibitor, 33DFTG, or vehicle alone and were processed for whole-mount immunofluorescence staining and Western blot analysis to quantify the density of blood vessels and markers of fibrosis. In addition, human umbilical vein endothelial cells (HUVECs) and primary human corneal fibroblasts were used to analyze the role of galectin-3 in the process of angiogenesis and fibrosis in vitro. RESULTS. Robust angiogenesis was observed in silver nitrate-cauterized corneas on day 5 post injury, and markedly increased corneal opacification was demonstrated in alkaline burn-injured corneas on days 7 and 14 post injury. Treatment with the inhibitor substantially reduced corneal angiogenesis and opacification with a concomitant decrease in a-smooth muscle actin (α-SMA) expression and distribution. In vitro studies revealed that 33DFTG inhibited VEGF-A-induced HUVEC migration and sprouting without cytotoxic effects. The addition of exogenous galectin-3 to corneal fibroblasts in culture induced the expression of fibrosis-related proteins, including α-SMA and connective tissue growth factor. CONCLUSIONS. Our data provide proof of concept that targeting galectin-3 by the novel, smallmolecule inhibitor, 33DFTG, ameliorates pathological corneal angiogenesis as well as fibrosis. These findings suggest a potential new therapeutic strategy for treating ocular disorders related to pathological angiogenesis and fibrosis.
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| 11. |
- Di, Guohu, et al.
(författare)
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Corneal Epithelium-Derived Neurotrophic Factors Promote Nerve Regeneration
- 2017
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Ingår i: Investigative Ophthalmology and Visual Science. - : ASSOC RESEARCH VISION OPHTHALMOLOGY INC. - 0146-0404 .- 1552-5783. ; 58:11, s. 4695-4702
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. To explore the neurotrophic factor expression in corneal epithelium and evaluate their effects on the trigeminal ganglion (TG) neurite outgrowth and corneal nerve regeneration in mice. METHODS. The expression of neurotrophic factors was compared among the intact, regenerating, and regenerated mouse corneal epithelium. Mouse primary TG neurons were treated with the conditioned medium of mouse corneal epithelial cells. Nerve growth factor (NGF) neutralizing antibody and glial cell-derived neurotrophic factor (GDNF) neutralizing antibody were used to evaluate their roles in mouse corneal nerve regeneration and TG neurite outgrowth. The promoting effects of NGF and GDNF for the corneal nerve regeneration were further evaluated in the diabetic mice. RESULTS. The expression of NGF and GDNF showed significant up-regulation in regenerating corneal epithelium and return to the preinjury levels in the regenerated epithelium, which was consistent with the progress of corneal subbasal nerve regeneration. The conditioned medium of corneal epithelial cells promoted the TG neurite outgrowth with extended branching and elongation. Furthermore, the blockage of either NGF or GDNF significantly impaired the promotion of the neurite outgrowth by the conditioned medium or the corneal nerve regeneration in normal mice. Moreover, the expression of NGF and GDNF was attenuated in the diabetic regenerating corneal epithelium as compared to that in normal mice, while exogenous NGF or GDNF supplement promoted the corneal epithelial and nerve regeneration in diabetic mice. CONCLUSIONS. Corneal epithelium expresses multiple neurotrophic factors, among which NGF and GDNF may play an important role in the corneal nerve regeneration.
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| 12. |
- Domellöf, Fatima Pedrosa, et al.
(författare)
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Desmin in extraocular muscles
- 2015
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Ingår i: Investigative Ophthalmology and Visual Science. - : ASSOC RESEARCH VISION OPHTHALMOLOGY. - 0146-0404 .- 1552-5783. ; 56:7
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 13. |
- Domellöf, Fatima Pedrosa, et al.
(författare)
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Sarcomere remodelling and gene expression profile changes following strabismus surgery
- 2018
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Ingår i: Investigative Ophthalmology and Visual Science. - : The Association for Research in Vision and Ophthalmology, Inc.. - 0146-0404 .- 1552-5783. ; 59:9
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Purpose : To investigate the extent and time axis of sarcomere remodeling and of gene expression profile changes following resection surgery in an animal model of strabismus surgery.Methods : The right superior rectus (SR) of 16 adult New Zealand white rabbits was resected 4 mm and reattached to the sclera, with ethical permission and following the animal care directives. The superior rectus muscle of 4 rabbits was collected 1, 2, 4 and 6 weeks after surgery. The SR of 4 control rabbits was also collected. The muscles were divided into two pieces longitudinally and one half was directly frozen for RNA extraction and the other half was stretched, fixed in 2% paraformaldehyde and frozen after sucrose cryoprotection. Serial longitudinal sections were processed for immunohistochemistry with antibodies against desmin. For each muscle section, the area comprising exclusively longitudinally sectioned myofibers was evaluated and the number of dividing sarcomeres present within that area was determined. RNA sequencing was performed with Illumina HiSeq 2500.Results : One week after surgery, the number of sarcomere divisions was 86.5/mm2 (range 30.9-152.7), after two weeks 72.0/ mm2 (42.5-95.9), after 4 weeks 95.7/ mm2 (37.4-161.3). After 6 weeks the number of sarcomere divisions (26.8/ mm2, 9.2-60.7) was similar to that of the control samples (26.0/ mm2, 6.0-66.9). RNA sequencing revealed up to 198 differentially expressed genes and further bioinformatics analysis is ongoing. Preliminary data indicate that the most significantly altered biological processes are those involved in extracellular matrix organization and inflammation, along with regulation of response and production of growth factors involved in muscle repair and regeneration.Conclusions : Signs of sarcomerogenesis were present during the first 4 weeks after resection of the superior rectus, suggesting that sarcomerogenesis plays a role in surgical failure due to recovery of muscle length. We suggest that medical approaches to limit this mechanism may be a desirable complementary therapy to strabismus surgery in the future.
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| 14. |
- Fast, Elizabeth, et al.
(författare)
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Eye vergence is limited by adaptation
- 2016
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Ingår i: Investigative Ophthalmology and Visual Science. - 0146-0404 .- 1552-5783. ; 57:12
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Tidskriftsartikel (refereegranskat)abstract
- Purpose : What limits vergence abilities? Current models propose that vergence movements are controlled by a phasic component, which responds to image disparities, and a slower tonic component that adapts based on the output of the phasic component. Adaptation in the tonic component frees the phasic component to compensate for further image disparities. Limits of vergence should arise when the tonic component can no longer adapt, but this failure has yet to be observed empirically. We tested the hypothesis that vergence limits would arise when there was evidence of a weakening adaptation in the tonic component.Methods : We adapted the vergence system of 6 subjects using a Wheatstone stereoscope. Binocular eye position was collected with an Eyelink 1000 eyetracker. Subjects binocularly viewed a detailed image of a natural scene. The image was initially presented at zero disparity, and moved laterally in one eye at a rate of 0.5°/s to reach 4° of eccentricity, where it remained for 5 m. Then the image moved in blocks, where each block comprised 1° of movement followed by 5 m of viewing at the new eccentricity. Blocks repeated until subjects experienced diplopia for 75% of a block. The eyetracker was used to calculate the angle between the eyes optical axes, which we term divergence. Phoria was measured every 30 s by calculating divergence when the image in one eye was replaced with a gray field for 5 s. As a control, subjects also viewed the display with one image moving continuously without the 5 m adaptation periods.Results : Subjects were able to fuse the images until eye divergence reached 7.14°, on average. We used phoria to estimate adaptation in the tonic component, with larger phorias indicating less adaptation. Adaptation, as measured by phoria, decreased over successive blocks (linear trend, p < 0.01). In addition, subjects reached a significantly greater divergence with adaptation than in the control condition (5.17°, p = 0.02).Conclusions : Our results support the hypothesis that the amount of vergence normal viewers can produce is limited by adaptation in the tonic component. In earlier blocks, when the tonic component adapted more fully, subjects were able to fuse the images, but in later blocks adaptation of the tonic component lagged behind, and diplopia was experienced. Future work can explore how the tonic component could adapt further, allowing the eyes to experience vergence angles unreachable in normal experience.
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| 15. |
- Fu, Z. J., et al.
(författare)
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Adiponectin Mediates Dietary Omega-3 Long-Chain Polyunsaturated Fatty Acid Protection Against Choroidal Neovascularization in Mice
- 2017
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Ingår i: Investigative Ophthalmology & Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 58:10, s. 3862-3870
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. Neovascular age-related macular degeneration (AMD) is a major cause of legal blindness in the elderly. Diets with omega3-long-chain-polyunsaturated-fatty-acid (omega 3-LCPUFA) correlate with a decreased risk of AMD. Dietary omega 3-LCPUFA versus omega 6-LCPUFA inhibits mouse ocular neovascularization, but the underlying mechanism needs further exploration. The aim of this study was to investigate if adiponectin (APN) mediated x omega 3-LCPUFA suppression of neovessels in AMD. METHODS. The mouse laser-induced choroidal neovascularization (CNV) model was used to mimic some of the inflammatory aspect of AMD. CNV was compared between wild-type (WT) and Apn(-/-) mice fed either otherwise matched diets with 2% x3 or 2% omega 6-LCPUFAs. Vldlr(-/-) mice were used to mimic some of the metabolic aspects of AMD. Choroid assay ex vivo and human retinal microvascular endothelial cell (HRMEC) proliferation assay in vitro was used to investigate the APN pathway in angiogenesis. Western blot for p-AMPK alpha/AMPK alpha and qPCR for Apn, Mmps, and IL-10 were used to define mechanism. RESULTS. omega 3-LCPUFA intake suppressed laser-induced CNV in WT mice; suppression was abolished with APN deficiency. omega 3-LCPUFA, mediated by APN, decreased mouse Mmps expression. APN deficiency decreased AMPK alpha phosphorylation in vivo and exacerbated choroid-sprouting ex vivo. APN pathway activation inhibited HRMEC proliferation and decreased Mmps. In Vldlr(-/-) mice, omega 3-LCPUFA increased retinal AdipoR1 and inhibited NV. omega 3-LCPUFA decreased IL-10 but did not affect Mmps in Vldlr(-/-) retinas. CONCLUSIONS. APN in part mediated omega 3-LCPUFA inhibition of neovascularization in two mouse models of AMD. Modulating the APN pathway in conjunction with a omega 3-LCPUFA-enriched-diet may augment the beneficial effects of omega 3-LCPUFA in AMD patients.
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| 16. |
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| 21. |
- Harandi, Vahid M, et al.
(författare)
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Unchanged neurotrophic factors and their receptors correlate with sparing in extraocular muscles in amyotrophic lateral sclerosis
- 2016
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Ingår i: Investigative Ophthalmology and Visual Science. - Rockville : The association for research in vision and ophthalmology. - 0146-0404 .- 1552-5783. ; 57:15, s. 6831-6842
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To investigate the impact of amyotrophic lateral sclerosis (ALS) on the extraocular muscles (EOMs) by examining the distribution of neurotrophic factors (NTFs) and their receptors in EOMs and limb muscles from ALS transgenic mice.Methods: Muscle samples collected from transgenic mice overexpressing human superoxide dismutase type 1 mutations (SOD1G93A, the most widely used mouse model of ALS) at 50 and 150 days as well as age-matched controls were analyzed with immunohistochemistry using antibodies against brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), neurotrophin-4/5 (NT-4), glial cell line-derived neurotrophic factor (GDNF), and the neurotrophin receptors p75NTR, tyrosine kinase (Trk) receptor TrkB and TrkC, and GDNF family receptor alpha-1 (GFRα-1).Results: There was an intrinsic difference in NTF expression between EOMs and limb muscles in control mice: EOMs presented significantly lower number of neuromuscular junctions (NMJs) labeled for BDNF and NT-4 at 50 days, and for BDNF and GDNF at 150 days, compared with the control limb muscles of corresponding age. In ALS transgenic mice at 150 days, NTF expression in limb muscles was significantly changed but not in EOMs: the limb muscles presented a significant decline in the number of NMJs labeled for BDNF, NT-4, GDNF, p75NTR, TrkB, and TrkC, which was not observed in EOMs.Conclusions: The significant differences in expression of NTFs on NMJs between EOMs and limb muscles in both control and ALS transgenic mice suggest that NTF may be involved in the pathogenesis of ALS and the resistance of EOMs to the disease.
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| 22. |
- Harun-Or-Rashid, Mohammad, et al.
(författare)
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Alpha2-Adrenergic-Agonist Brimonidine Stimulates Negative Feedback and Attenuates Injury-Induced Phospho-ERK and Dedifferentiation of Chicken Müller Cells
- 2015
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 56:10, s. 5933-5945
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Tidskriftsartikel (refereegranskat)abstract
- Purpose:Retinal injury induces Müller cell dedifferentiation by activating extracellular signal-regulated kinase (ERK) signaling. Stimulation of α2-adrenergic receptors protects against injury but also activates ERK in Müller cells. The purpose of this work was to study the effect of α2-adrenergic signaling on injury-induced ERK and Müller cell dedifferentiation. We tested the hypothesis that α2-stimulation triggers negative feedback regulation of the injury-induced ERK pathway that attenuates Müller cell dedifferentiation.Methods:Chicken retina injured by N-methyl-D-aspartate and cultured primary Müller cells were stimulated by the α2-adrenergic agonist brimonidine. Immunostaining, quantitative RT-PCR, and Western blot techniques in combination with receptor blockers were used for analysis of the cellular responses.Results:Alpha2-adrenergic receptor stimulation attenuated injury-induced ERK activation and dedifferentiation of Müller cells as seen by decreased phospho-ERK, expression of transitin, and retinal progenitor cell genes. The attenuation was concomitant with a synergistic upregulation of several negative ERK-signal feedback regulators including ERK-phosphatases, Raf1-, and growth factor receptor–binding proteins. The results were also seen in cultures of primary Müller cells.Conclusions:Alpha2-adrenergic signaling on Müller cells elicits an intracellular attenuation of the injury response that comprises negative ERK-signaling feedback leading to attenuated Müller cell dedifferentiation. The implications of this study are that adrenergic stress signals may directly modulate glial function in retina and that α2-adrenergic receptor pharmacology may be used to control glial injury response.
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| 23. |
- He, Min, et al.
(författare)
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Artificial Polymeric Scaffolds as Extracellular Matrix Substitutes for Autologous Conjunctival Goblet Cell Expansion
- 2016
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Ingår i: Investigative Ophthalmology and Visual Science. - : ASSOC RESEARCH VISION OPHTHALMOLOGY INC. - 0146-0404 .- 1552-5783. ; 57:14, s. 6134-6146
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. We fabricated and investigated polymeric scaffolds that can substitute for the conjunctival extracellular matrix to provide a substrate for autologous expansion of human conjunctival goblet cells in culture. METHODS. We fabricated two hydrogels and two silk films: (1) recombinant human collagen (RHC) hydrogel, (2) recombinant human collagen 2-methacryloylxyethyl phosphorylcholine (RHC-MPC) hydrogel, (3) arginine-glycine-aspartic acid (RGD) modified silk, and (4) poly-D-lysine (PDL) coated silk, and four electrospun scaffolds: (1) collagen, (2) poly(acrylic acid) (PAA), (3) poly(caprolactone) (PCL), and (4) poly(vinyl alcohol) (PVA). Coverslips and polyethylene terephthalate (PET) were used for comparison. Human conjunctival explants were cultured on scaffolds for 9 to 15 days. Cell viability, outgrowth area, and the percentage of cells expressing markers for stratified squamous epithelial cells (cytokeratin 4) and goblet cells (cytokeratin 7) were determined. RESULTS. Most of cells grown on all scaffolds were viable except for PCL in which only 3.6 +/- 2.2% of the cells were viable. No cells attached to PVA scaffold. The outgrowth was greatest on PDL-silk and PET. Outgrowth was smallest on PCL. All cells were CK7-positive on RHCMPC while 84.7 +/- 6.9% of cells expressed CK7 on PDL-silk. For PCL, 87.10 +/- 3.17% of cells were CK7-positive compared to PET where 67.10 +/- 12.08% of cells were CK7-positive cells. CONCLUSIONS. Biopolymer substrates in the form of hydrogels and silk films provided for better adherence, proliferation, and differentiation than the electrospun scaffolds and could be used for conjunctival goblet cell expansion for eventual transplantation once undifferentiated and stratified squamous cells are included. Useful polymer scaffold design characteristics have emerged from this study.
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| 24. |
- Henrysson, Ida, et al.
(författare)
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Binocular Vision, Reading Ability and Associated Symptoms in School Children
- 2015
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Ingår i: Investigative Ophthalmology and Visual Science. - 0146-0404 .- 1552-5783. ; 56:7, s. 530-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Purpose: The purpose of this study was to investigate relationship between binocular vision, reading ability and any associated symptoms in School Children.Methods: The study was conducted in a School in western Sweden. A sample of 54 Children aged between 10 and 12 years were invited to participate in this study. A consent form and a letter with information was sent to their parents. Children with at least 20/25 and N6 visual acuity and good Stereopsis were included. After receiving consent forms, 27 Children participated in all the measurements. Amplitude of accommodation was measured using push-up method both monocularly and binocularly. Accommodative facility was measured using ± 2.00 D flippers at 40 cm both monocularly and binocularly. Near point of convergence was measured using a Royal Air Force (RAF) ruler and both break and recovery points were documented. All the Children performed a group of reading ability tests to detect whether they have any reading difficulties. A questionnaire called "The College of Optometrists in Vision Development Quality of Life (COVD-QOL)" was filled by their parents together with their Children. A score of 20 or more is considered as symptomatic.Results: Mean amplitude of accommodation was OD 10.8 ± 4.0 D, OS 11.8 ± 4.1 D and OU 14.2 ± 3.7 D. Amplitude of accommodation was low in terms of Hofstetter's formula. Based on age, 59% of the Children were below expected value. The accommodative facility was lower than expected, with mean values of OD 5.5 ± 4.0 cpm, OS 5.5 ± 4.0 cpm and OU 5.0 ± 3.5 cpm. Mean near point of convergence was 6.0 ± 5.4 cm for break and 6.6 ± 5.9 cm for recovery. In the reading ability tests all the Children had normal values. Three Children received ≥ 20 points on the symptom questionnaire COVD-QOL, which is considered to be high. All of these three Children had values below normal limits for the amplitude of accommodation and/or the accommodative facility. Regression analysis showed no significant correlation between binocular vision tests, reading ability and symptom score (r < 0.6; p > 0.05).Conclusions: Amplitude of accommodation and accommodative facility was lower than expected values for their age. Near point of convergence values reached the expected normal level. There was no significant correlation between binocular vision tests, reading ability and associated symptoms in this sample of Swedish Children.
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| 25. |
- Hernández-Moreno, Laura, et al.
(författare)
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The Portuguese version of the activity inventory
- 2015
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Ingår i: Investigative Ophthalmology and Visual Science. - 0146-0404 .- 1552-5783. ; 56:7
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To characterize interventions needed by the population with visual impairment or to assess interventions in vision rehabilitation validated and standardized instruments used in different cultural contexts are necessary. The aim of this work was to characterize the functional status of a sample of people with visual impairment with the Portuguese version of the activity inventory (AI)Methods: A group of participants in the study Prevalence and Costs of Visual Impairment in Portugal (PC-VIP) was recruit to face-to-face interviews and the activity inventory was administered. The AI examines 50 goals split between three objectives: social functioning, recreation and daily living. Goals rated ‘not important’ were skipped, but for all other goals the participant was asked to rate its difficulty on a five point scale ranging from ‘not difficult’ to ‘impossible without help’. The difficulty responses were Rasch analysed (Winsteps v3.81.0) to produce a continuous measure of visual ability (AI score). Additional information about distance and near visual acuity (ETDRS scale), contrast sensitivity (MARS test) and critical print size (MNREAD test) was collected.Results: A total of 94 persons participated in this study. Some participants were not able to read or recognize letters due to their poor vision or poor literacy and were excluded from further analysis. Data reported here are from 62 participants, median age 63y (range=12-85) and the most common cause of visual impairment were retinal diseases. Mean presenting acuity in the better eye was 0.93logMAR (SD=0.5). The mean difficulty (item measure) in the AI was -0.33 logits (SD=0.96). The most difficult items were "sew or do needlework", "read the newspaper", "drive" and the easiest items were "provide care for a pet", "eat your meals", "use the restroom in a public place". The mean ability score (person measures) was 1.11 logits (SD=2.04). The ability measures in the AI were correlated with distance visual acuity (r=-0.57, p<.001), near visual acuity (r=-0.66, p<0.001), contrast sensitivity (r=0.62, p<.001) and critical print size (r=-0.60, p<.001).Conclusions: Our results indicate that the AI scores in a sample of people Portuguese people with visual impairment were in line with what has been found in other cultural contexts. The visual ability measured by the AI was correlated with visual function assessed by different visual tests, which shows that this instrument can be used with confidence.
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| 26. |
- Holmström, Gerd, et al.
(författare)
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Ten years of ROP-screening and treatment in Sweden - consideration of modified screening guidelines based on a national quality register
- 2019
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Ingår i: Investigative Ophthalmology and Visual Science. - : The Association for Research in Vision and Ophtalmology. - 0146-0404 .- 1552-5783. ; 60:9
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Purpose : Description of ten years of national ROP-screening and treatment in Sweden and evaluation of the national screening program for ROP.Methods : The study is based on a national register for ROP, SWEDROP, with around 96% coverage. According to Swedish guidelines, all infants born at 30 weeks gestational age (GA) or less, as well as children born later but being extremely sick, should be screened for ROP during the neonatal period. Birth data are validated in the Swedish neonatal quality register, SNQ.Results : During the ten-year period between 2008 and 2017, 7257 infants with a GA of 30 weeks or less were registered in SWEDROP and 46.294 examinations were performed, of which 5.328 (11.5%) in infants born in gestational week 30. Mean GA was 27.6 w (range 21-30 w) and mean BW was 1116 g (range 390-2405 g). Overall, during the ten years, ROP was found in 31.8% (range 26.8-36.8%) and treatment for ROP was performed in 6% (range 4.1-7.7%) of the screened infants. Only nine infants with GA 28 w and four with GA 29 w were treated for ROP. No infant with GA 30 w was treated. Eighty-two per cent (361/441) of the treated infants had laser only and 17.7% (78/441) were treated with Anti-VEGF, alone (17 infants) or in combination with laser and/or other treatment.Conclusions : SWEDROP is a national register for ROP with a high national coverage. The incidence of ROP and frequency of treatment remained similar over the ten-year period. Only 13 infants born at 28 – 29 weeks GA and no child born at 30 w GA were treated for ROP. Modification of guidelines is considered, with lowering the upper limit of screening with one week, i.e. to less than 30 weeks GA. During the ten-year study period, this would have resulted in a reduction of 1680 infants (23.2%) screened for ROP and of 5.328 (11.5%) examinations.
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| 27. |
- Ingling, Allen W, et al.
(författare)
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Fixation stability readily obtained from confocal color fundus imaging
- 2015
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Ingår i: Investigative Ophthalmology and Visual Science. - 0146-0404 .- 1552-5783. ; 56:7, s. 515-515
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Tidskriftsartikel (refereegranskat)abstract
- PurposeStabile fixation underpins most visual tasks such as reading, and is important for accurate assessment of visual function and treatment. Retinal imaging instruments average images over time to improve the signal to noise ratio, discarding useful eye movement data. We determined whether the frame-to-frame motion of the retina during non-mydriatic color fundus imaging could provide fixation stability measures, e.g. Bivariate Contour Ellipse Area (BCEA). MethodsNon-mydriatic color fundus images were acquired using the Digital Light Ophthalmoscope (DLO). Twenty subjects with varied fundus pigmentation were tested without mydriasis. The DLO uses a digital light projector with LED light sources to provide the illumination for both confocal imaging and fixation stimuli. The DLO projects a series of lines across the fundus that is synchronized to the 2D CMOS sensor, providing high contrast confocal imaging. Monochromatic 40 deg images were acquired with alternating red and green LED illumination at 14.3 Hz and overlayed to present a pseudo-color image to the operator in real time. To reduce pupil constriction and patient discomfort, the green LED was long-pass filtered with a 570 nm filter. A 1.5mm entrance pupil and time-averaged power of <30 uW were used. Images were aligned automatically with custom software (MATLAB) using cross-correlation and 2D translation. A canvas of twice the image size was used to allow image alignment despite moderate eye movements. Blinks and large saccades were discarded and BCEA was computed. ResultsThe image alignment algorithm successfully aligned nearly all the frames, rejecting 3.7%, and allowing fixation stability to be computed from color fundus image data. The BCEA for 1 standard deviation was 2.97 log minarc2 for all subjects and both the red and yellow-orange illumination. There was no difference between the BCEA for red or yellow-orange illumination (t = .86). ConclusionsThe color DLO records sufficiently high quality images to reliably calculate measures of fixation stability. Despite recruiting an especially challenging population that included dark fundi, small pupils, high refractive errors, and media issues, we achieved success in all subjects tested to date.
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| 28. |
- Jakobsson, Gunnar, et al.
(författare)
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Increased Levels of Inflammatory Immune Mediators in Vitreous From Pseudophakic Eyes
- 2015
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Ingår i: Investigative Ophthalmology & Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 56:5, s. 3407-3414
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. To determine if pseudophakic eyes have an increased and sustained level of inflammatory immune mediators in the vitreous compared to phakic eyes. METHODS. Vitreous fluid samples were obtained from 73 patients undergoing elective pars plana vitrectomy (PPV) as a result of a macular hole, epiretinal membrane, vitreous macular traction, or vitreous floaters. Forty eyes were pseudophakic and had previously undergone uncomplicated cataract surgery, ranging from a few months to several years prior to PPV. The vitreous samples were analyzed for 29 different inflammatory immune mediators using multiplex bead immunoassays. RESULTS. A total of 14 cytokines (eotaxin, interferon-c-induced protein-10 [IP-10], monocyte chemotactic protein-1 [MCP-1], macrophage derived chemokine [MDC], macrophage inflammatory protein [MIP]-1 alpha, MIP-1 beta, thymus activation regulated chemokine [TARC], IL-12p40, IL-15, IL-16, IL-7, VEGF, IL-6, and IL-8) were detected in the vitreous of both study groups. Using multiple linear regression analysis, pseudophakiawas significantly correlated with higher levels of vitreous immune mediators compared to phakia. Elevated vitreous levels were estimated to decrease over time for IL-6, IL-8, IL-15, IL-16, and VEGF, though they remained elevated for many months and even years compared to the levels detected in phakic eyes. CONCLUSIONS. This is the first study to demonstrate that cataract surgery and pseudophakia can induce increased vitreous levels of a substantial range of inflammatory immune mediators. The elevated levels seem to be maintained for a long period of time. These increased levels of cytokines may be involved in inflammatory processes leading to several complications to cataract surgery, both early and late.
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| 29. |
- Johannesson, Gauti, et al.
(författare)
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Age-dependency of ocular parameters - a cross sectional study of young and old healthy subjects
- 2015
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology. - 0146-0404 .- 1552-5783. ; 56:7
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)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.
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| 30. |
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| 31. |
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| 32. |
- Kristiansen, Martin, et al.
(författare)
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Blood flow rate of ophthalmic artery in patients with normal tension glaucoma and healthy controls
- 2018
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Ingår i: Investigative Ophthalmology and Visual Science. - : The Association for Research in Vision and Ophthalmology. - 0146-0404 .- 1552-5783. ; 59:9
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- 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.
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| 33. |
- Lagali, Neil, et al.
(författare)
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Focused Tortuosity Definitions Based on Expert Clinical Assessment of Corneal Subbasal Nerves
- 2015
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Ingår i: Investigative Ophthalmology and Visual Science. - : ASSOC RESEARCH VISION OPHTHALMOLOGY INC. - 0146-0404 .- 1552-5783. ; 56:9, s. 5102-5109
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. We examined agreement among experts in the assessment of corneal subbasal nerve tortuosity. METHODS. Images of corneal subbasal nerves were obtained from investigators at seven sites (Auckland, Boston, Linkoping, Manchester, Oslo, Rostock, and Sydney) using laser-scanning in vivo confocal microscopy. A set of 30 images was assembled and ordered by increasing tortuosity by 10 expert graders from the seven sites. In a first experiment, graders assessed tortuosity without a specific definition and performed grading three times, with at least 1 week between sessions. In a second experiment, graders assessed the same image set using four focused tortuosity definitions. Intersession and intergrader repeatability for the experiments were determined using the Spearman rank correlation. RESULTS. Expert graders without a specific tortuosity definition had high intersession (Spearman correlation coefficient 0.80), but poor intergrader (0.62) repeatability. Specific definitions improved intergrader repeatability to 0.79. In particular, tortuosity defined by frequent small-amplitude directional changes (short range tortuosity) or by infrequent large-amplitude directional changes (long range tortuosity), indicated largely independent measures and resulted in improved repeatability across the graders. A further refinement, grading only the most tortuous nerve in a given image, improved the average correlation of a given graders ordering of images with the group average to 0.86 to 0.90. CONCLUSIONS. Definitions of tortuosity specifying short or long-range tortuosity and considering only the most tortuous nerve in an image improved the agreement in tortuosity grading among a group of expert observers. These definitions could improve accuracy and consistency in quantifying subbasal nerve tortuosity in clinical studies.
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| 34. |
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| 35. |
- Lagali, Neil S, 1973-, et al.
(författare)
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Reduced Corneal Nerve Fiber Density in Type 2 Diabetes by Wide-Area Mosaic Analysis
- 2017
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Ingår i: Investigative Ophthalmology and Visual Science. - : The Assocation for Research in Vision and Ophthalmology. - 0146-0404 .- 1552-5783. ; 58:14, s. 6318-6327
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. To determine if corneal subbasal nerve plexus (SBP) parameters derived from wide-area depth-corrected mosaic images are associated with type 2 diabetes.METHODS. One hundred sixty-three mosaics were produced from eyes of 82 subjects by laser-scanning in vivo confocal microscopy (IVCM). Subjects were of the same age, without (43 subjects) or with type 2 diabetes (39 subjects). Mosaic corneal nerve fiber length density (mCNFL) and apical whorl corneal nerve fiber length density (wCNFL) were quantified and related to the presence and duration of diabetes (short duration < 10 years and long duration ≥10 years).RESULTS. In mosaics with a mean size of 6 mm2 in subjects aged 69.1 ± 1.2 years, mCNFL in type 2 diabetes was reduced relative to nondiabetic subjects (13.1 ± 4.2 vs. 15.0 ± 3.2 mm/mm2, P = 0.018). Also reduced relative to nondiabetic subjects was mCNFL in both short-duration (14.0 ± 4.0 mm/mm2, 3.2 ± 3.9 years since diagnosis) and long-duration diabetes (12.7 ± 4.2 mm/mm2, 15.4 ± 4.2 years since diagnosis; ANOVA P =0.023). Lower mCNFL was associated with presence of diabetes (P =0.032) and increased hemoglobin A1c (HbA1c) levels (P = 0.047). By contrast, wCNFL was unaffected by diabetes or HbA1c (P > 0.05). Global SBP patterns revealed marked degeneration of secondary nerve fiber branches outside the whorl region in long-duration diabetes.CONCLUSIONS. Wide-area mosaic images provide reference values for mCNFL and wCNFL and reveal a progressive degeneration of the SBP with increasing duration of type 2 diabetes.
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| 36. |
- Landsend, Erlend C. S., et al.
(författare)
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Characteristics and Utility of Fundus Autofluorescence in Congenital Aniridia Using Scanning Laser Ophthalmoscopy
- 2019
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Ingår i: Investigative Ophthalmology and Visual Science. - : ASSOC RESEARCH VISION OPHTHALMOLOGY INC. - 0146-0404 .- 1552-5783. ; 60:13, s. 4120-4128
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. To investigate fundus autofluorescence (FAF) and other fundus manifestations in congenital aniridia. METHODS. Fourteen patients with congenital aniridia and 14 age- and sex-matched healthy controls were examined. FAF images were obtained with an ultra-widefield scanning laser ophthalmoscope. FAF intensity was quantified in the macular fovea and in a macular ring surrounding fovea and related to an internal reference within each image. All aniridia patients underwent an ophthalmologic examination, including optical coherence tomography and slitlamp biomicroscopy. RESULTS. Mean age was 28.4 +/- 15.0 years in both the aniridia and control groups. Fovea could be defined by subjective assessment of FAF images in three aniridia patients (21.4%) and in all controls (P = 0.001). Mean ratio between FAF intensity in the macular ring and fovea was 1.01 +/- 0.15 in aniridia versus 1.18 +/- 0.09 in controls (P = 0.034). In aniridia, presence of foveal hypoplasia evaluated by biomicroscopy correlated with lack of foveal appearance by subjective analyses of FAF images (P = 0.031) and observation of nystagmus (P = 0.009). CONCLUSIONS. Aniridia patients present a lower ratio between FAF intensity in the peripheral and central macula than do healthy individuals. Both subjective and objective analyses of FAF images are useful tools in evaluation of foveal hypoplasia in aniridia.
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| 37. |
- Landsend, Erlend C. S., et al.
(författare)
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The Level of Inflammatory Tear Cytokines is Elevated in Congenital Aniridia and Associated with Meibomian Gland Dysfunction
- 2018
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Ingår i: Investigative Ophthalmology and Visual Science. - : ASSOC RESEARCH VISION OPHTHALMOLOGY INC. - 0146-0404 .- 1552-5783. ; 59:5, s. 2197-2204
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. To investigate the tear cytokine profile in congenital aniridia, and correlate cytokine levels with ophthalmologic findings. METHODS. We examined 35 patients with aniridia and 21 healthy controls. Tear fluid was collected with Schirmer I test and capillary tubes from each eye, and the concentration of 27 inflammatory cytokines determined using multiplex bead assay. Eyes of all participants were examined with tests for dry eye disease, including evaluation of meibomian glands (meibography). Differences in cytokine levels between the two groups were analyzed, and correlations between cytokine concentrations and ophthalmologic findings in the aniridia group investigated. RESULTS. The concentrations of six tear cytokines were significantly higher in aniridia patients than controls in both eyes, and included interleukin 1 beta (IL-1 beta), IL-9, IL-17A; eotaxin; basic fibroblast growth factor (bFGF/FGF2); and macrophage inflammatory protein 1 alpha (MIP-1 alpha/ CCL3). The ratio between the anti-inflammatory IL-1RA and the proinflammatory IL-1 beta was significantly lower in patients than controls in both eyes (P = 0.005 right eye and P = 0.001 left eye). Increasing concentration of IL-1 beta, IL-9, IL-17A, FGF2, and MIP-1 alpha correlated with parameters for meibomian gland dysfunction (MGD) in the aniridia group, including increasing atrophy of meibomian glands, and shorter break-up time of the tear film. CONCLUSIONS. A number of pro-inflammatory cytokines are significantly elevated in tear fluid from aniridia patients, and correlate with parameters for MGD in aniridia. Increased inflammation of the ocular surface may be a factor in the development of MGD in aniridia patients, and explain the high prevalence of MGD and dry eye disease in these patients.
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| 38. |
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| 39. |
- Lindström, Mona, et al.
(författare)
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Pax7-Positive Cells/Satellite Cells in Human Extraocular Muscles
- 2015
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 56:10, s. 6132-6143
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. We quantified and investigated the distribution of Pax7-positive cells/satellite cells (SCs) in the human extraocular muscles (EOMs). METHODS. An immunofluorescence multiple-marker method simultaneously combining two SC markers (Pax7, NCAM), detection of the basement membrane (laminin) and cell nuclei (4',6-diamidino-2-phenylindole [DAPI]), was used on the anterior, middle, and posterior portions of EOMs from five healthy donors. Pax7-positive cell and SC content, myonuclear content, myofiber cross-sectional area, and myonuclear domain were analyzed in single cross-sections. Between 3915 and 13,536 myofibers per muscle cross-section and myofibers from the entire EOM cross-section were analyzed for quantification of Pax7-positive cells per myofiber (Pax7/F).RESULTS. The number of Pax7/F in the human EOMs varies along the length of the muscle with twice as high Pax7/F in the anterior part of the EOMs, but within the range of what has been previously reported for normal adult limb muscles. Furthermore, there are Pax7-positive cells in positions other than the classical SC position and the myonuclear domain size of adult EOMs is noticeably smaller than that previously reported for other adult skeletal muscles.CONCLUSIONS. Previous data on differences in Pax7-positive cell/SC abundance between EOMs and limb muscles must be reconsidered and the characteristics of different Pax7-positive cell populations further investigated. Higher numbers of Pax7-positive cells in the anterior portion of the EOMs may have a bearing for strabismus surgery involving sectioning of the muscle fibers.
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| 40. |
- Liu, Jing-Xia, et al.
(författare)
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A novel type of multiterminal motor endplate in human extraocular muscles
- 2018
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Ingår i: Investigative Ophthalmology and Visual Science. - Rockville : The Association for Research in Vision and Ophthalmology. - 0146-0404 .- 1552-5783. ; 59:1, s. 539-548
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To investigate the relation between type of motor endplate, acetylcholine receptor (AChR) subunit composition, and fiber types in human extraocular muscles (EOMs).Methods: EOM samples collected from subjects aged 34 to 82 years were serially sectioned and processed for immunohistochemistry, with specific antibodies against different myosin heavy chain (MyHC) isoforms, neurofilament, synaptophysin, and adult epsilon (ε) and fetal gamma (γ) AChR subunits as well as α-bungarotoxin.Results: A novel type of motor endplate consisting of large, multiterminal en plaque endings was found in human EOMs, in addition to the previously well-described single en plaque and multiple en grappe endplates. Such novel endplates were abundant but exclusively observed in myofibers lacking MyHC slow and fast IIa but containing MyHC extraocular (MyHCeom), isoforms. Multiple en grappe endings were found only in myofibers containing MyHC slow-tonic isoform and contained fetal γ AChR subunit. Adult ε and fetal γ AChR subunits, alone or combined, were found in the multiterminal endplates. Distinct AChR subunits were present in adjacent motor endplates of a given myofiber containing MyHCeom.Conclusions: Human EOMs have a more complex innervation pattern than previously described, comprising also a novel type of multiterminal motor endplate present in myofibers containing MyHCeom. The heterogeneity in AChR subunit composition in a given myofiber suggests the possible presence of polyneuronal innervation in human EOMs.
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| 41. |
- Louwies, T., et al.
(författare)
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Separate and combined effects of hypoxia and horizontal bed rest on retinal blood vessel diameters
- 2016
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology Inc.. - 0146-0404 .- 1552-5783. ; 57:11, s. 4927-4932
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. To assess the separate and combined effects of exposure to prolonged and sustained recumbency (bed rest) and hypoxia on retinal microcirculation. METHODS. Eleven healthy male subjects (mean 6 SD age = 27 ± 6 years; body mass index [BMI] = 23.7 ± 3.0 kg m-2) participated in a repeated-measures crossover design study comprising three 21-day interventions: normoxic bed rest (NBR; partial pressure of inspired O2, PiO2 = 133.1 ± 0.3 mm Hg); hypoxic ambulation (HAMB; PiO2 = 90.0 6 0.4 mm Hg), and hypoxic bed rest (HBR; PiO2 = 90.0 ± 0.4 mm Hg). Central retinal arteriolar (CRAE) and venular (CRVE) equivalents were measured at baseline and at regular intervals during each 21- day intervention. RESULTS. Normoxic bed rest caused a progressive reduction in CRAE, with the change in CRAE relative to baseline being highest on day 15 (ΔDCRAE = -7.5 µm; 95% confidence interval [CI]: -10.8 to -4.2; P < 0.0001). Hypoxic ambulation resulted in a persistent 21-day increase in CRAE, reaching a maximum on day 4 (DCRAE = 9.4 µm; 95% CI: 6.0-12.7; P < 0.0001). During HBR, the increase in CRAE was highest on day 3 (ΔDCRAE = 4.5 µm; 95% CI: 1.2-7.8; P = 0.007), but CRAE returned to baseline levels thereafter. Central retinal venular equivalent decreased during NBR and increased during HAMB and HBR. The reduction in CRVE during NBR was highest on day 1 (ΔDCRVE = -7.9 µm; 95 CI: -13.3 to -2.5), and the maximum ΔDCRVE during HAMB (24.6 µm; 95% CI: 18.9-30.3) and HBR (15.2 µm; 95% CI: 9.8-20.5) was observed on days 10 and 3, respectively. CONCLUSIONS. The diameters of retinal blood vessels exhibited a dynamic response to hypoxia and bed rest, such that retinal vasodilation was smaller during combined bed rest and hypoxia than during hypoxic exposure.
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| 42. |
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| 43. |
- Macedo, António Filipe, et al.
(författare)
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Anti-saccades in early stages of multiple sclerosis
- 2015
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Ingår i: Investigative Ophthalmology and Visual Science. - 0146-0404 .- 1552-5783. ; 56:7
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Eye movements disability is common finding in multiple sclerosis (MS) but the exact stage at which changes are visible is not clear. The aim of study was to assess if anti-saccade (AS) planning and execution are altered at early stages of the disease.Methods: A total of 48 participants with MS selected by a neurologist (JJC) at Hospital de Braga and 52 controls participated in this study. Inclusion criteria: relapsing-remitting course, EDSS≤3, 1 month or more without MS crisis, and normal or corrected visual acuity. Exclusion criteria (MS and Control): cognitive impairment, traumatic brain injury or stroke. The mean age in the MS group was 37y and 33y in the control group. Eye movements were monitored using a binocular infrared eyetracker running at 250Hz(RED250, SMI Gmb Germany), precision <0.4deg, stimuli were presented in a 22 monitor (Dell P2210). Code for running the experiment and data analysis was written using the Matlab (Mathworks Inc). Participants were seated in a room dim light at 74cm from the monitor and head movements were minimized by a headband. The task was to fixate, after a variable period between steady fixation and the stimulus of 1250ms or 1600ms, participants looked as quickly as possible for the opposite direction where the target (a 30x30mm cross) was presented (anti-saccade movement). Each subject performed 40 trails.Results: The main results were the proportion of the directional errors (wherein the participant voluntarily looked for the wrong side), and latencies for: i) anti-saccades, ii) pro-saccades (movement in the same direction of the stimulus) and iii) correction (reaction time that the participant takes from the error fixation until to start the movement). The mean number of errors was 28%(SD=19) in MS group and 16%(SD=11) in the control group, mean difference 12%, t(74)=3.83, p<.001. Anti-saccades latency was 330msec (SD=61) in the MS group and 294ms(SD=59) in the control group, mean difference 36ms, F(1,98)=10.99, p<.05. The mean of the correction latency value was 178ms(SD=111) in the MS group and 129ms(SD=107) in the control group with a mean difference of 49ms, F(1,98)=6, p<.05. No statistically significant differences were found in accuracy and pro-saccade latency between groups.Conclusions: This study shows that anti-saccades latency and errors are increased at early stages of multiple sclerosis. Anti-saccades might be a sensitive tool to assess functional status in people with this condition.
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| 44. |
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| 45. |
- Marques, Ana Patricia, et al.
(författare)
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Estimating the cost of visual impairment : initial results
- 2015
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Ingår i: Investigative Ophthalmology and Visual Science. - 0146-0404 .- 1552-5783. ; 56:7
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Vision loss can have a substantial human and economic impact on individuals and society that include disability, loss of productivity and reduction in quality of life. The purpose of this study was to estimate economic burden of visual impairment in Portugal.Methods: A prevalence-based cost of illness approach was adopted to estimate costs of vision impairment. We estimated direct medical costs and indirect economic costs. Direct medical hospital costs were determined using a bottom up approach. For those meeting the inclusion criteria (visual acuity of 20/40 or 0.5decimal or worse in the better eye and/or visual field of less than 20deg) we estimated direct costs by collecting information from administrative records that included: physician’s office visits, emergency and outpatient visits. We developed a survey based in parts of the annotated cost questionnaire-HERU Discussion Paper N.03/01 (UK Working Party on Patient Costs) and the Service Receipt Inventory-European Version. Using the questionnaire that we developed, in face-to-face interviews, we collect direct medical expenditures supported by patients that included: costs with medical prescriptions, low vision aids and devices. With the same questionnaire we collected information for indirect costs calculations. Indirect costs were calculated by estimating the value of productivity losses including employment participation, absenteeism and caregiver costs.Results: Results presented here correspond to 442 patients that met the inclusion criteria. The four main causes of visual impairment in this sample were Diabetic Retinopathy, Cataract, Glaucoma and Age-related macular degeneration. Direct medical hospital costs were accountable for 12% of total costs calculated. Patient expenditures represented 25% of expenses with visual impairment and indirect costs corresponded to 63% of the total. From this data we estimated that the average annual direct cost per patient with VI was 958 euro and average annual indirect cost was 1655 euro.Conclusions: With the instruments and methodology that was adopted we were able quantify direct medical hospital costs as well as indirect costs of visual impairment. Results of this study show that more than half of the costs with VI are indirect. This highlights that particular attention should be given to costs that arise for individuals with vision loss.
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| 46. |
- McLoon, Linda K., et al.
(författare)
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Composition, architecture, and functional implications of the connective tissue network of the extraocular muscles
- 2018
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Ingår i: Investigative Ophthalmology and Visual Science. - Rockville : The Association for Research in Vision and Ophthalmology. - 0146-0404 .- 1552-5783. ; 59:1, s. 322-329
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: We examined the pattern and extent of connective tissue distribution in the extraocular muscles (EOMs) and determined the ability of the interconnected connective tissues to disseminate force laterally.Methods: Human EOMs were examined for collagens I, III, IV, and VI; fibronectin; laminin; and elastin using immunohistochemistry. Connective tissue distribution was examined with scanning electron microscopy. Rabbit EOMs were examined for levels of force transmission longitudinally and transversely using in vitro force assessment.Results: Collagens I, III, and VI localized to the endomysium, perimysium, and epimysium. Collagen IV, fibronectin, and laminin localized to the basal lamina surrounding all myofibers. All collagens localized similarly in the orbital and global layers throughout the muscle length. Elastin had the most irregular pattern and ran longitudinally and circumferentially throughout the length of all EOMs. Scanning electron microscopy showed these elements to be extensively interconnected, from endomysium through the perimysium to the epimysium surrounding the whole muscle. In vitro physiology demonstrated force generation in the lateral dimension, presumably through myofascial transmission, which was always proportional to the force generated in the longitudinally oriented muscles.Conclusions: A striking connective tissue matrix interconnects all the myofibers and extends, via perimysial connections, to the epimysium. These interconnections are significant and allow measurable force transmission laterally as well as longitudinally, suggesting that they may contribute to the nonlinear force summation seen in motor unit recording studies. This provides strong evidence that separate compartmental movements are unlikely as no region is independent of the rest of the muscle.
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| 49. |
- Mukwaya, Anthonny, et al.
(författare)
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Repeat Corneal Neovascularization is Characterized by More Aggressive Inflammation and Vessel Invasion Than in the Initial Phase
- 2019
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Ingår i: Investigative Ophthalmology and Visual Science. - Rockville, MD, United States : Association for Research in Vision and Ophthalmology. - 0146-0404 .- 1552-5783. ; 60:8, s. 2990-3001
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Treatment of corneal neovascularization can lead to vessel regression and recovery of corneal transparency. Here, we examined the response of the cornea to a repeated stimulus after initial vessel regression comparing the second wave of neovascularization with the first.Methods: Corneal neovascularization was induced by surgical suture placement in the rat cornea for 7 days, followed by suture removal and a 30-day regression period. Corneas were then re-sutured and examined for an additional 4 days. Longitudinal slit-lamp imaging, in vivo confocal microscopy, and microarray analysis of global gene expression was conducted to assess the inflammatory and neovascularization response. Inhibitory effect of topical dexamethasone for repeat neovascularization was assessed.Results: After initial robust neovascularization, 30 days of regression resulted in the recovery of corneal transparency; however, a population of barely functional persistent vessels remained at the microscopic level. Upon re-stimulation, inflammatory cell invasion, persistent vessel dilation, vascular invasion, and gene expression of Vegfa, Il1β, Il6, Ccl2, Ccl3, and Cxcl2 all doubled relative to initial neovascularization. Repeat neovascularization occurred twice as rapidly as initially, with activation of nitric oxide and reactive oxygen species, matrix metalloproteinase, and leukocyte extravasation signaling pathways, and suppression of anti-inflammatory LXR/RXR signaling. While inhibiting initial neovascularization, a similar treatment course of dexamethasone did not suppress repeat neovascularization.Conclusions: Persistent vessels remaining after the initial resolution of neovascularization can rapidly reactivate to facilitate more aggressive inflammation and repeat neovascularization, highlighting the importance of achieving and confirming complete vessel regression after an initial episode of corneal neovascularization.
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| 50. |
- Mönestam, Eva
(författare)
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Long-time outcome of cataract surgery-20 years results from a prospective study
- 2018
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Ingår i: Investigative Ophthalmology and Visual Science. - : The Association for Research in Vision and Ophthalmology. - 0146-0404 .- 1552-5783. ; 59:9
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Purpose: This study reports the change, over a 20-year period, in best-corrected visual acuity (BCVA), subjective visual function (VF-14 questionnaire), and YAG-frequency after cataract surgery.Methods: This population-based prospective study reviewed 106 patients (79% of survivors), who underwent cataract surgery during a 1-year period 20 years previously (1997). All patients answered the same visual function questionnaire (VF-14) preoperatively, 4 months postoperatively, 5, 10, 15 and 20 years after surgery. Most patients (90%; 95/106; 70% of survivors) also had a routine ocular examination including BCVA and low contrast visual acuity (VA) 10% and 2.5%. Mean age at the time of surgery was 59 years (range 36-79) and 95% had a three-piece Acrysof® MA60BM implanted.Results: Twenty years after surgery the median BCVA of the operated eye had deteriorated to a median of 0.06 (logMAR) (Snellen acuity: 20/23) from 0.0 (logMAR) (20/20) postoperatively, (p=0.001). Sixty-one percent of the patients (58/95) had less than 0.1 logMAR units worsening of BCVA compared with postoperatively. Seventeen percent of the patients (16/95) had worse BCVA 20 years after surgery compared with the preoperative VA. Forty-two percent (45/106) had no deterioration in subjective visual function (VF-14), and mean VF-14 score 20 years after surgery was 92 (range 33-100). The majority of patients (78%;82/106) had 10 points decline or less and 6 percent of the patients (6/106) had a worsening of more than 30 points. 61% of the patients (58/95) had never had Nd:YAG laser capsulotomy. In 7% of the patients (7/95) no cataract surgery had occurred in the fellow eye.Conclusions: These prospective population-based, follow-up data provides estimates of extended long-term visual results. The effectiveness of cataract extraction, in offering good long-term visual rehabilitation for the majority of the patients, is confirmed. The extent and distribution of loss in subjective visual function is comparable to the outcome 10 and 15 years after surgery. Age-related macular degeneration remained the most common comorbidity causing large functional loss also 20 years after cataract surgery. Surprisingly, despite the low age at cataract surgery and the long time span, only a minority of patients had needed treatment for posterior capsular opacification.
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