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Erik Nilsson, Sven
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Publications (10 of 27) Show all publications
Frennesson, C. & Nilsson, S. E. (2014). A three-year follow-up of ranibizumab treatment of exudative AMD: impact on the outcome of carrying forward the last acuity observation in drop-outs. Acta Ophthalmologica, 92(3), 216-220
Open this publication in new window or tab >>A three-year follow-up of ranibizumab treatment of exudative AMD: impact on the outcome of carrying forward the last acuity observation in drop-outs
2014 (English)In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 92, no 3, p. 216-220Article in journal (Refereed) Published
Abstract [en]

Abstract. Purpose: To analyse a 3-year clinical patient cohort of ranibizumab treatment of exudative age-related macular degeneration (AMD), to investigate the impact on visual outcome of carrying forward the last acuity observation in drop-outs and to explore possible differences between the early and the late phase of the study. Methods: A retrospective study of 312 eyes with neovascular AMD. The patients were followed up monthly, received three initial monthly injections of 0.5 mg ranibizumab and were re-treated pro re nata (PRN). Time-domain optical coherence tomography (TD-OCT) was used until spectral-domain (SD)-OCT was introduced during the last year of enrolment. Sixty-five patients were discontinued from the study. Primary outcome: change in best corrected visual acuity (BCVA). Results: Best corrected visual acuity was 58.4 (CI 56.9-59.9) ETDRS (Early Treatment Diabetic Retinopathy Study) letters. At three months, it had increased by 4.1 letters (p = 0.0004), at 12 months by 1.8 letters, at 24 months by 1.0 letter and at 36 months by 0.1 letter. However, if the last available acuity of drop-outs was carried forward one step and included, acuity had increased by 3.9 letters at 3 months (p less than 0.0001) and by 1.0 letter at 12 months but had decreased by 3.8 letters at 24 months (p = 0.019) and by 4.1 letters (p = 0.003) at 36 months. At 24 months, the result was significantly (p = 0.030) less favourable when drop-outs were included. In patients enrolled during the late phase, BCVA was 59.3 (CI 56.7-62.0). It had increased by 5.7 letters (p less than 0.0001) at three months and by 5.8 letters at 12 months (p = 0.0016). In patients enrolled during the early phase, BCVA was 57.9 (CI 55.0-60.8). At three months, it had increased by 3.5 letters (p = 0.0008), but at 12 months, it had decreased by 2.3 letters (ns). The result at 12 months was significantly (p = 0.0033) better for the late than for the early phase. The number of injections was also significantly (p = 0.011) higher in the late phase. Adverse events were similar to those in earlier clinical trials. Conclusions: The results of this 3-year cohort showed that the initial average acuity could be maintained over 36 months, which was comparable to those of many other clinical cohorts. However, if the last available acuity of drop-outs was carried forward one step and included, the acuity figures would have fallen significantly. The results in patients enrolled during the late phase of the study were fairly similar to those in clinical trials.

Place, publisher, year, edition, pages
Wiley, 2014
Keywords
drop-outs; long-term results; ranibizumab treatment; exudative AMD
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-106671 (URN)10.1111/aos.12091 (DOI)000334532900011 ()
Available from: 2014-05-21 Created: 2014-05-19 Last updated: 2017-12-05
Frennesson, C., Wadelius, C. & Nilsson, S. E. (2014). Best vitelliform macular dystrophy in a Swedish family: genetic analysis and a seven-year follow-up of photodynamic treatment of a young boy with choroidal neovascularization. Acta Ophthalmologica, 92(3), 238-242
Open this publication in new window or tab >>Best vitelliform macular dystrophy in a Swedish family: genetic analysis and a seven-year follow-up of photodynamic treatment of a young boy with choroidal neovascularization
2014 (English)In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 92, no 3, p. 238-242Article in journal (Refereed) Published
Abstract [en]

Abstract. Purpose: To determine the mutation in a Swedish family with Best disease (vitelliform macular dystrophy; VMD) and to investigate the short- and long-term effects of photodynamic treatment (PDT) on subretinal neovascularization in a young boy. Methods: The five members of three generations of a family with VMD underwent a thorough ophthalmological examination, including best-corrected visual acuity (VA), visual field, colour vision, biomicroscopy of the posterior segment (dilated), fundus photography and electro-oculography (EOG). For the proband, an eleven-year-old boy, his father and grandfather, dark adaptation test, angiography and electroretinography (ERG) were also performed. After PCR amplification, the genotype was determined by cleavage with restriction enzyme, specific for the W93C allele. Results: Four family members had an abnormal EOG response. All showed the W93C mutation in the VMD2 gene. Visual acuity ranged from 20/20 to 20/250. The fundus manifestations varied from minor pigmentary changes over egg yolk-like lesions to chorioretinal atrophy, and fluorescein angiography showed corresponding pathology. In the proband, VA decreased during follow-up from 0.5 (20/40) to 0.08 (20/250) due to a subfoveal neovascularization with haemorrhage, and PDT with visudyne was begun. The haemorrhage resolved within 2 months, and after three treatments, VA had increased to 0.25 (20/80). One year later, acuity had improved to 0.5 (20/40), and this result was stable throughout the 7 years of the follow-up. Conclusion: The mutation was determined to be W93C, the most common mutation in VMD in Sweden. In an eleven-year-old boy with subretinal neovascularization, PDT seemed to be beneficial also in a long-term follow-up.

Place, publisher, year, edition, pages
Wiley, 2014
Keywords
Best disease; genetic analysis; photodynamic treatment; choroidal neovascularization; vitelliform macular degeneration
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-106672 (URN)10.1111/aos.12142 (DOI)000334532900020 ()
Available from: 2014-05-21 Created: 2014-05-19 Last updated: 2017-12-05
Karlsson, M., Frennesson, C., Gustafsson, T., Brunk, U., Erik Nilsson, S. & Kurz, T. (2013). Autophagy of iron-binding proteins may contribute to the oxidative stress resistance of ARPE-19 cells. Experimental Eye Research, 116, 359-365
Open this publication in new window or tab >>Autophagy of iron-binding proteins may contribute to the oxidative stress resistance of ARPE-19 cells
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2013 (English)In: Experimental Eye Research, ISSN 0014-4835, E-ISSN 1096-0007, Vol. 116, p. 359-365Article in journal (Refereed) Published
Abstract [en]

The objective of this study was to elucidate possible reasons for the remarkable resistance of human retinal pigment epithelial (RPE) cells to oxidative stress. Much oxidative damage is due to hydrogen peroxide meeting redox-active iron in the acidic and reducing lysosomal environment, resulting in the production of toxic hydroxyl radicals that may oxidize intralysosomal content, leading to lipofuscin (LF) formation or, if more extensive, to permeabilization of lysosomal membranes. Formation of LF is a risk factor for age-related macular degeneration (AMD) and known to jeopardize normal autophagic rejuvenation of vital cellular biomolecules. Lysosomal membrane permeabilization causes release of lysosomal content (redox-active iron, lytic enzymes), which may then cause cell death. Total cellular and lysosomal low-mass iron of cultured, immortalized human RPE (ARPE-19) cells was compared to that of another professional scavenger cell line, J774, using atomic absorption spectroscopy and the cytochemical sulfide-silver method (SSM). It was found that both cell lines contained comparable levels of total as well as intralysosomal iron, suggesting that the latter is mainly kept in a non-redox-active state in ARPE-19 cells. Basal levels and capacity for upregulation of the iron-binding proteins ferritin, metallothionein and heat shock protein 70 were tested in both cell lines using immunoblotting. Compared to J774 cells, ARPE-19 cells were found to contain very high basal levels of all these proteins, which could be even further upregulated following appropriate stimulation. These findings suggest that a high basal expression of iron-binding stress proteins, which during their normal autophagic turnover in lysosomes may temporarily bind iron prior to their degradation, could contribute to the unusual oxidative stress-resistance of ARPE-19 cells. A high steady state influx of such proteins into lysosomes would keep the level of lysosomal redox-active iron permanently low. This, in turn, should delay intralysosomal accumulation of LF in RPE cells, which is known to reduce autophagic turnover as well as uptake and degradation of worn out photoreceptor tips. This may explain why severe LF accumulation and AMD normally do not develop until fairly late in life, in spite of RPE cells being continuously exposed to high levels of oxygen and light, as well as large amounts of lipid-rich material.

Place, publisher, year, edition, pages
Elsevier, 2013
Keywords
oxidative stress, ARPE-19, retinal pigment epithelium, iron, metallothionein, HSP70, ferritin, age-related macular degeneration
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-102718 (URN)10.1016/j.exer.2013.10.014 (DOI)000327562500041 ()
Note

Funding Agencies|Crown Princess Margaretas Foundation for the Visually Handicapped||Edvin Jordan Foundation for Ophthalmological Research||Linkoping University Hospital Research Fund (ALF)||

Available from: 2013-12-19 Created: 2013-12-19 Last updated: 2018-01-11
Frennesson, C., Nilsson, U., Bourghardt Peebo, B. & Nilsson, S. E. (2010). Significant improvements in near vision, reading speed, central visual field and related quality of life after ranibizumab treatment of wet age-related macular degeneration. ACTA OPHTHALMOLOGICA, 88(4), 420-425
Open this publication in new window or tab >>Significant improvements in near vision, reading speed, central visual field and related quality of life after ranibizumab treatment of wet age-related macular degeneration
2010 (English)In: ACTA OPHTHALMOLOGICA, ISSN 1755-375X, Vol. 88, no 4, p. 420-425Article in journal (Refereed) Published
Abstract [en]

Purpose: To investigate the effects on near visual acuity, reading speed, central visual field and related quality of life of ranibizumab treatment of wet age-related macular degeneration (AMD). Methods: The study was a prospective, non-comparative consecutive case series, followed for 3 months and investigator-driven. Thirty eyes of 30 patients with wet AMD were included, mean age 75 years (range 69-95 years). In addition to a full ophthalmological examination - including best-corrected visual acuity (BCVA; Early Treatment Diabetic Research Study chart), fundus biomicroscopy, fundus photography, fluorescein angiography, indocyanine green angiography (occult cases) and ocular coherence tomography - near visual acuity, reading speed, central visual field and quality of life for related activities were also investigated at baseline and at 3 months after ranibizumab treatment. Results: Mean BCVA increased from 62 +/- 11 to 66 +/- 14 letters at 3 months (7%; p = 0.018). Near vision improved from 9 +/- 5 to 6 +/- 3 points (33%; p = 0.0006) and reading speed increased from 59 +/- 40 to 85 +/- 50 words/min (44%; p andlt; 0.0001). The mean deviation from normal of the visual field improved from -9 +/- 7 to -6 +/- 5 dB (33%; p andlt; 0.0001). Quality of life improved for distance activities from 54 +/- 28 to 63 +/- 28 points (17%; p andlt; 0.0001) but significantly (p = 0.024) more for near activities, from 49 +/- 26 to 63 +/- 26 points (29%; p andlt; 0.0001). Reading newspaper text in the group in which the better eye was treated showed the highest increase in quality of life score of all: 116%. Conclusion: The increase in BCVA after ranibizumab treatment is well established. The present study also showed significant improvements in other important visual qualities, such as near visual acuity, reading speed, central visual field and several activities influencing quality of life. The improvement was greater for near activities than for distance activities. Therefore, the beneficial effects of ranibizumab treatment shown here are more extensive than those reported previously.

Place, publisher, year, edition, pages
Blackwell Publishing Ltd, 2010
Keywords
best-corrected visual acuity, near vision, quality of life, ranibizumab treatment, reading speed, visual field, wet AMD
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-57424 (URN)10.1111/j.1755-3768.2009.01576.x (DOI)000278182000007 ()
Available from: 2010-06-18 Created: 2010-06-18 Last updated: 2010-06-18
Karlsson, M., Kurz, T., Brunk, U. T., Nilsson, S. E. & Frennesson, C. I. (2010). What does the commonly used DCF test for oxidative stress really show?. Biochemical Journal, 428(2), 183-90
Open this publication in new window or tab >>What does the commonly used DCF test for oxidative stress really show?
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2010 (English)In: Biochemical Journal, ISSN 0264-6021, E-ISSN 1470-8728, Vol. 428, no 2, p. 183-90Article in journal (Refereed) Published
Abstract [en]

H(2)DCF-DA (dihydrodichlorofluorescein diacetate) is widely used to evaluate 'cellular oxidative stress'. After passing through the plasma membrane, this lipophilic and non-fluorescent compound is de-esterified to a hydrophilic alcohol [H(2)DCF (dihydrodichlorofluorescein)] that may be oxidized to fluorescent DCF (2',7'-dichlorofluorescein) by a process usually considered to involve ROS (reactive oxygen species). It is, however, not always recognized that, being a hydrophilic molecule, H(2)DCF does not cross membranes, except for the outer fenestrated mitochondrial ones. It is also not generally realized that oxidation of H(2)DCF is dependent either on Fenton-type reactions or on unspecific enzymatic oxidation by cytochrome c, for neither superoxide, nor H(2)O(2), directly oxidizes H(2)DCF. Consequently, oxidation of H(2)DCF requires the presence of either cytochrome c or of both redox-active transition metals and H(2)O(2). Redox-active metals exist mainly within lysosomes, whereas cytochrome c resides bound to the outer side of the inner mitochondrial membrane. Following exposure to H(2)DCF-DA, weak mitochondrial fluorescence was found in both the oxidation-resistant ARPE-19 cells and the much more sensitive J774 cells. This fluorescence was only marginally enhanced following short exposure to H(2)O(2), showing that by itself it is unable to oxidize H(2)DCF. Cells that were either exposed to the lysosomotropic detergent MSDH (O-methylserine dodecylamide hydrochloride), exposed to prolonged oxidative stress, or spontaneously apoptotic showed lysosomal permeabilization and strong DCF-induced fluorescence. The results suggest that DCF-dependent fluorescence largely reflects relocation to the cytosol of lysosomal iron and/or mitochondrial cytochrome c.

Keywords
age-related macular degeneration (AMD), 2', 7'-dichlorofluorescein (DCF), lysosome, oxidative stress, reactive oxygen species (ROS), transition metal.
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-56466 (URN)10.1042/BJ20100208 (DOI)20331437 (PubMedID)
Available from: 2010-05-17 Created: 2010-05-17 Last updated: 2017-12-12
Kurz, T., Karlsson, M., Brunk, U., Erik Nilsson, S. & Frennesson, C. (2009). ARPE-19 retinal pigment epithelial cells are highly resistant to oxidative stress and exercise strict control over their lysosomal redox-active iron. AUTOPHAGY, 5(4), 494-501
Open this publication in new window or tab >>ARPE-19 retinal pigment epithelial cells are highly resistant to oxidative stress and exercise strict control over their lysosomal redox-active iron
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2009 (English)In: AUTOPHAGY, ISSN 1554-8627, Vol. 5, no 4, p. 494-501Article in journal (Refereed) Published
Abstract [en]

Normal retinal pigment epithelial (RPE) cells are postmitotic, long-lived and basically not replaced. Daily, they phagocytose substantial amounts of lipid-rich material (photoreceptor outer segment discs), and they do so in the most oxygenated part of the body-the retina. One would imagine that this state of affairs should be associated with a rapid formation of the age pigment lipofuscin (LF). However, LF accumulation is slow and reaches significant amounts only late in life when, if substantial, it often coincides with or causes age-related macular degeneration. LF formation occurs inside the lysosomal compartment as a result of iron-catalyzed peroxidation and polymerization. This process requires phagocytosed or autophagocytosed material under degradation, but also the presence of redox-active low mass iron and hydrogen peroxide. To gain some information on how RPE cells are able to evade LF formation, we investigated the response of immortalized human RPE cells (ARPE-19) to oxidative stress with/without the protection of a strong iron-chelator. The cells were found to be extremely resistant to hydrogen peroxide-induced lysosomal rupture and ensuing cell death. This marked resistance to oxidative stress was not explained by enhanced degradation of hydrogen peroxide, but to a certain extent further increased by the potent lipophilic iron chelator STH. The cells were also able to survive, and even replicate, at high concentrations of SIH and showed a high degree of basal autophagic flux. We hypothesize that RPE cells have a highly developed capacity to keep lysosomal iron in a nonredox-active form, perhaps by pronounced autophagy of iron-binding proteins in combination with an ability to rapidly relocate low mass iron from the lysosomal compartment.

Keywords
age-related macular degeneration, hydrogen peroxide, iron, iron chelation, lipofuscin, lysosomal stability, lysosomes, macrophage, oxidative stress, retinal pigment epithelial cells
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-18569 (URN)10.4161/auto.5.4.7961 (DOI)
Available from: 2009-06-01 Created: 2009-06-01 Last updated: 2014-10-24
Frennesson, C., Bek, T., Jaakkola, A. & Erik Nilsson, S. (2009). Prophylactic laser treatment of soft drusen maculopathy: a prospective, randomized Nordic study. ACTA OPHTHALMOLOGICA, 87(7), 720-724
Open this publication in new window or tab >>Prophylactic laser treatment of soft drusen maculopathy: a prospective, randomized Nordic study
2009 (English)In: ACTA OPHTHALMOLOGICA, ISSN 1755-375X, Vol. 87, no 7, p. 720-724Article in journal (Refereed) Published
Abstract [en]

Purpose: This study aimed to investigate whether mild laser treatment of soft drusen maculopathy might reduce the incidence of choroidal neovascularization (CNV) and/or significantly reduce loss of visual acuity compared with outcomes in a control group. Methods: A total of 135 patients (mean age 70.4 years) were randomized into a treatment group of 67 subjects and a control group of 68 subjects. The treatment group was subdivided into a group of 54 subjects with bilateral soft drusen and a group of 13 subjects with unilateral soft drusen in the study eye and advanced AMD in the fellow eye. The control group was subdivided into a bilateral group of 54 subjects and a unilateral group of 14 subjects. Sub-threshold or barely visible laser spots were scattered on and between drusen in the posterior pole. Inclusion of patients was stopped prematurely as other studies did not show any benefit from the treatment. Mean follow-up time was 3.7 years. Results: More CNVs developed in the treated group (4/54 eyes in the bilateral group, 3/13 eyes in the unilateral group; 7/67 eyes in total) than in the control group (3/54 eyes in the bilateral group, 2/14 eyes in the unilateral group; 5/68 eyes in total) but these differences were not statistically significant for either the bilateral or unilateral groups (p = 0.20-0.32). No CNV developed in the bilateral treated group before 4 years of follow-up. Visual acuity was significantly reduced from baseline to the last follow-up in all groups (p andlt; 0.0001-0.02) except the unilateral control group (p = 0.08), but there were no significant differences between the treated and control groups for either the bilateral or unilateral groups (p = 0.17-0.97). Conclusions: Mild prophylactic laser treatment of soft drusen maculopathy was neither beneficial nor harmful and cannot be recommended.

Keywords
age-related maculopathy, laser treatment, prophylactic measure, soft drusen
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-51488 (URN)10.1111/j.1755-3768.2008.01396.x (DOI)
Available from: 2009-11-04 Created: 2009-11-04 Last updated: 2009-11-04
Nilsson, S. E. & Frennesson, C. (2008). Antioxidants and macular degeneration. Läkartidningen, 105(11), 836-836
Open this publication in new window or tab >>Antioxidants and macular degeneration
2008 (English)In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 105, no 11, p. 836-836Article in journal (Other academic) Published
Abstract [en]

  

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-44949 (URN)78410 (Local ID)78410 (Archive number)78410 (OAI)
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13
Frennesson, C. & Nilsson, S. E. (2007). In eccentric viewing, reading performance is better when using the upper compared to the lower retina. In: ARVO E-abstract 3551 Invest ophthalmol vis sci,2007.
Open this publication in new window or tab >>In eccentric viewing, reading performance is better when using the upper compared to the lower retina
2007 (English)In: ARVO E-abstract 3551 Invest ophthalmol vis sci,2007, 2007Conference paper, Published paper (Other academic)
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-42372 (URN)63299 (Local ID)63299 (Archive number)63299 (OAI)
Available from: 2009-10-10 Created: 2009-10-10
Frennesson, C. & Nilsson, S. E. (2007). The superior retina performs better than the inferior retina when reading with eccentric viewing: A comparison in normal volunteers. Acta Ophthalmologica Scandinavica, 85(8), 868-870
Open this publication in new window or tab >>The superior retina performs better than the inferior retina when reading with eccentric viewing: A comparison in normal volunteers
2007 (English)In: Acta Ophthalmologica Scandinavica, ISSN 1395-3907, E-ISSN 1600-0420, Vol. 85, no 8, p. 868-870Article in journal (Refereed) Published
Abstract [en]

Purpose: Patients with an absolute central scotoma, such as in age-related macular degeneration, need to use eccentric viewing for reading. In the present study, we investigated whether there are differences in reading performance between the superior and inferior retina. Methods: Twelve volunteers with normal vision, aged 25-58 years and able to maintain stable eccentric viewing, were studied in a scanning laser ophthalmoscope while reading a line of text, 6 degrees above or below a fixation line (series A). The text, properly magnified above threshold, was scrolled at a speed of 60 words/min. The number of words missed or incorrectly read in 1 min as well as words read when occasionally fixating the text was counted. In series B, a random letter text was superimposed upon the fixation line (i.e. at 6 degrees from the original line of text) to see whether this would disturb reading. In series C, the random letter text was moved away from the fixation line to a distance of 12 degrees from the original line of text. The entire programme was repeated in reverse order, and the mean value of the two series was used for calculations, which were carried out using Student's two-sided t-test. Results: In all series of experiments, the number of errors was significantly lower when using the superior retina compared with the inferior retina (A: p = 0.006, B: p = 0.042, C: p = 0.009). The addition of the random letter line of text at 6 or 12 degrees did not disturb reading performance significantly. There was no significant difference between the superior and inferior retina in terms of visual acuity. Conclusions: In eccentric viewing, reading performance was significantly better when using the superior retina compared with the inferior retina. A line of random letter text at a distance of 6 or 12 degrees from the original line of text did not disturb reading significantly. © 2007 The Authors Journal Compilation © 2007 Acta Ophthalmol Scand.

Keywords
Eccentric viewing, Normal volunteers, Reading, Scanning laser ophthalmoscope, Superior and inferior retina
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-47577 (URN)10.1111/j.1600-0420.2007.00984.x (DOI)
Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-13
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