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  • 1.
    Frennesson, Christina
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oftalmologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Rekonstruktionscentrum, Ögonkliniken US/LiM.
    Bek, Toke
    Aarhus University Hospital.
    Jaakkola, Aino
    Helsinki University Hospital.
    Erik Nilsson, Sven
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oftalmologi. Linköpings universitet, Hälsouniversitetet.
    Prophylactic laser treatment of soft drusen maculopathy: a prospective, randomized Nordic study2009Ingår i: ACTA OPHTHALMOLOGICA, ISSN 1755-375X, Vol. 87, nr 7, s. 720-724Artikel i tidskrift (Refereegranskat)
    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.

  • 2.
    Frennesson, Christina
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neurovetenskap. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Sinnescentrum, Ögonkliniken US/LiM.
    Nilsson, Sven Erik
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neurovetenskap. Linköpings universitet, Hälsouniversitetet.
    A three-year follow-up of ranibizumab treatment of exudative AMD: impact on the outcome of carrying forward the last acuity observation in drop-outs2014Ingår i: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 92, nr 3, s. 216-220Artikel i tidskrift (Refereegranskat)
    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.

  • 3.
    Frennesson, Christina
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Oftalmologi. Östergötlands Läns Landsting, Rekonstruktionscentrum, Ögonkliniken US.
    Nilsson, Sven Erik
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Oftalmologi.
    Angiogeneshämmare vid neovaskulär åldersrelaterad makuladegeneration - lovande terapi eller risk för oönskade effekter?2005Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 102, s. 1969-1969Artikel i tidskrift (Övrigt vetenskapligt)
  • 4.
    Frennesson, Christina
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Oftalmologi. Östergötlands Läns Landsting, Rekonstruktionscentrum, Ögonkliniken US.
    Nilsson, Sven Erik
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Oftalmologi.
    Encouraging results of photodynamic therapy with Visudyne in a clinical patient material of age-related macular degeneration2004Ingår i: Acta Ophthalmologica Scandinavica, ISSN 1395-3907, E-ISSN 1600-0420, Vol. 82, nr 6, s. 645-650Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: To investigate the effects of photodynamic therapy (PDT) on subfoveal choroidal neovascularization (CNV) in age-related macular degeneration (AMD) in a Swedish patient material with smaller lesions than those investigated in the TAP (Treatment of Age-related Macular Degeneration with Photodynamic Therapy) and VIP (Verteporfin in Photodynamic Therapy) Studies. Methods: Photodynamic therapy with verteporfin was performed according to the results and recommendations of the TAP and VIP Studies. The patients were followed up for 12 months and retreatment was performed every 12 weeks when leakage from CNV was present. Of the 100 eyes in the first 100 patients with a follow-up period of 12 months, 59% had a predominantly classic lesion, 36% had an occult-only lesion and 5% had a minimally classic lesion. The greatest linear dimension (GLD) was ≤3 NIPS (Macular Photocoagulation Study) disc diameters (DD) in 73%, 39% and 20% of lesions, respectively, for the three groups. The actual lesion area was ≤3 MPS disc areas (DA) in 85%, 50% and 40% of lesions, respectively. There was a positive correlation (p < 0.05) between the duration of symptoms and GLD, as well as between the duration of symptoms and the lesion area (p < 0.02). Results: At 12 months, visual acuity had remained stable or increased by ≥3 lines (ETDRS) in 61% of patients with predominantly classic lesions, in 61% of patients with occult-only lesions and in 60% of patients with minimally classic lesions. Leakage had stopped after 2.9 ± 0.9 treatments in 77% of the total group of patients. Conclusion: The visual outcome was comparable to those of the TAP and VIP Studies (p > 0.3). Regarding the effect on leakage, however, our results are far better than those of the TAP and VIP Studies. The proportion of patients in which leakage had stopped was almost three times that of the TAP (27%) and VIP (26%) Studies. It seems likely that this difference was caused by the fact that the lesions in our study were much smaller, on average, than those in the TAP and VIP Studies.

  • 5.
    Frennesson, Christina
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oftalmologi. Östergötlands Läns Landsting, Rekonstruktionscentrum, Ögonkliniken US/LiM.
    Nilsson, Sven Erik
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oftalmologi.
    Encouraging results with photodynamic treatment (PDT) in a clinical patient material of age-related macular degeneration (AMD) and other diagnoses: Leakage stopped with fewer treatments than in the Tap and Vip studies2002Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 43, s. 593-Konferensbidrag (Övrigt vetenskapligt)
  • 6.
    Frennesson, Christina
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Oftalmologi. Östergötlands Läns Landsting, Rekonstruktionscentrum, Ögonkliniken US.
    Nilsson, Sven Erik
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Oftalmologi.
    In eccentric viewing, reading performance is better when using the upper compared to the lower retina2007Ingår i: ARVO E-abstract 3551 Invest ophthalmol vis sci,2007, 2007Konferensbidrag (Övrigt vetenskapligt)
  • 7.
    Frennesson, Christina
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oftalmologi. Östergötlands Läns Landsting, Rekonstruktionscentrum, Ögonkliniken US/LiM.
    Nilsson, Sven Erik
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oftalmologi.
    The superior retina performs better than the inferior retina when reading with eccentric viewing: A comparison in normal volunteers2007Ingår i: Acta Ophthalmologica Scandinavica, ISSN 1395-3907, E-ISSN 1600-0420, Vol. 85, nr 8, s. 868-870Artikel i tidskrift (Refereegranskat)
    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.

  • 8.
    Frennesson, Christina
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Oftalmologi. Östergötlands Läns Landsting, Rekonstruktionscentrum, Ögonkliniken US/LiM.
    Nilsson, Sven Erik
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Oftalmologi.
    Åldersrelaterad makuladegeneration - nya möjligheter för profylax och terapi2002Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 99, s. 3194-3197Artikel i tidskrift (Övrigt vetenskapligt)
  • 9.
    Frennesson, Christina
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oftalmologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Rekonstruktionscentrum, Ögonkliniken US/LiM.
    Nilsson, Ulla
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oftalmologi. Linköpings universitet, Hälsouniversitetet.
    Bourghardt Peebo, Beatrice
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oftalmologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Rekonstruktionscentrum, Ögonkliniken US/LiM.
    Nilsson, Sven Erik
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oftalmologi. Linköpings universitet, Hälsouniversitetet.
    Significant improvements in near vision, reading speed, central visual field and related quality of life after ranibizumab treatment of wet age-related macular degeneration2010Ingår i: ACTA OPHTHALMOLOGICA, ISSN 1755-375X, Vol. 88, nr 4, s. 420-425Artikel i tidskrift (Refereegranskat)
    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.

  • 10.
    Frennesson, Christina
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neurovetenskap. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Sinnescentrum, Ögonkliniken US/LiM.
    Wadelius, Claes
    Uppsala University, Sweden .
    Nilsson, Sven Erik
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neurovetenskap. Linköpings universitet, Hälsouniversitetet.
    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 neovascularization2014Ingår i: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 92, nr 3, s. 238-242Artikel i tidskrift (Refereegranskat)
    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.

  • 11.
    Friström, Björn
    et al.
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Oftalmologi. Linköpings universitet, Hälsouniversitetet.
    Nilsson, Sven Erik G.
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Oftalmologi. Linköpings universitet, Hälsouniversitetet.
    A double masked comparison of the intraocular pressure reducing effect of latanoprost 0.005% and 0.001% administered once daily in open angle glaucoma and ocular hypertension1997Ingår i: British Journal of Ophthalmology, ISSN 0007-1161, E-ISSN 1468-2079, Vol. 81, nr 10, s. 867-870Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIM To compare the intraocular pressure (IOP) reducing effect of latanoprost 0.005% and 0.001%.

    METHODS Twenty four patients with glaucoma or ocular hypertension were randomised into two groups. Twelve patients (group 1) were given latanoprost 0.005% once daily for 4 weeks and then latanoprost 0.001% once daily for the following 4 weeks. Twelve patients (group 2) were given latanoprost 0.001% once daily for 4 weeks and then latanoprost 0.005% for the following 4 weeks.

    RESULTS There was a significant IOP reduction from baseline in both groups on day 28 as well as on day 56. When the results from both groups were used for calculations, the mean IOP reduction from baseline after 4 weeks of treatment with latanoprost 0.005% (day 28 or 56) was 9.6 (SD 3.3) mm Hg (35.0%). After 4 weeks of treatment with latanoprost 0.001%, the IOP reduction (day 28 or 56) was 7.6 (3.4) mm Hg (27.7%). The difference in IOP reduction between the two concentrations was 2.0 (2.3) mm Hg (p<0.001).

    CONCLUSIONS Latanoprost 0.005% was more effective than latanoprost 0.001% in reducing IOP. Even the lower concentration was surprisingly effective, and potentially may be of importance for use in clinical practice. Furthermore, it is at present unknown whether the increase in iris pigmentation seen in certain patients treated with latanoprost 0.005% is dose dependent and might be less pronounced with latanoprost 0.001%. Long term studies with a larger number of patients are required in order to answer this question.

  • 12.
    Friström, Björn
    et al.
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Oftalmologi. Linköpings universitet, Hälsouniversitetet.
    Nilsson, Sven Erik G.
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Oftalmologi. Linköpings universitet, Hälsouniversitetet.
    Interaction of PhXA41, a New Prostaglandin Analogue, With Pilocarpine: A Study on Patients With Elevated Intraocular Pressure1993Ingår i: Archives of ophthalmology (1960), ISSN 0003-9950, Vol. 111, nr 5, s. 662-665Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective.  —To evaluate the effects of PhXA41, a new prostaglandin analogue, on the intraocular pressure (IOP) in patients receiving pilocarpine treatment and the effects of pilocarpine in patients receiving PhXA41 treatment.

    Design.  —Twenty patients with ocular hypertension were randomized into two parallel groups. The treatment period was 2 weeks. Ten patients in group 1 were given PhXA41 twice daily during week 1 and, in addition, pilocarpine three times daily during week 2. Ten patients in group 2 received pilocarpine three times daily during week 1 and PhXA41 twice daily in addition during week 2. PhXA41 was used in a concentration of 0.006%, and pilocarpine was given in a concentration of 2%.

    Main Outcome Measures.  —In group 1, the mean IOP on day 0 was 25.1 mm Hg; on day 7,19.1 mm Hg; and on day 14,17.6 mm Hg. In group 2, the mean IOP on day 0 was 23.8 mm Hg; on day 7,20.4 mm Hg; and on day 14,17.7 mm Hg.

    Results.  —PhXA41 had a clinically significant IOP-lowering effect (23.4% reduction on day 7 as compared with baseline day (P<.001). The corresponding value with pilocarpine was 14.3% (P<.001). When pilocarpine was added to PhXA41, the additional IOP reduction was 7.4% (P<.01) compared with 14.2% (P<.01) when PhXA41 was added to pilocarpine. The two groups were found to have an almost equal reduction in IOP on day 14 (group 1,29.4%; group 2, 26.6%). No serious adverse reactions were seen. Some conjunctival hyperemia in the PhXA41-treated eyes was noted on day 7, as compared with the pilocarpine-treated eyes, but there were few complaints of discomfort.

    Conclusions.  —This study indicated that PhXA41 could be useful in the treatment of glaucoma, as monotherapy, or in certain cases in combination with pilocarpine.

  • 13.
    Karlsson, Markus
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neurovetenskap. Linköpings universitet, Hälsouniversitetet.
    Frennesson, Christina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neurovetenskap. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Sinnescentrum, Ögonkliniken US/LiM.
    Gustafsson, Therese
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neurovetenskap. Linköpings universitet, Hälsouniversitetet.
    Brunk, Ulf
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Hälsouniversitetet.
    Erik Nilsson, Sven
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neurovetenskap. Linköpings universitet, Hälsouniversitetet.
    Kurz, Tino
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Hälsouniversitetet.
    Autophagy of iron-binding proteins may contribute to the oxidative stress resistance of ARPE-19 cells2013Ingår i: Experimental Eye Research, ISSN 0014-4835, E-ISSN 1096-0007, Vol. 116, s. 359-365Artikel i tidskrift (Refereegranskat)
    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.

  • 14.
    Karlsson, Markus
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oftalmiatrik. Linköpings universitet, Hälsouniversitetet.
    Kurz, Tino
    Linköpings universitet, Institutionen för medicin och hälsa, Farmakologi. Linköpings universitet, Hälsouniversitetet.
    Brunk, Ulf T.
    Linköpings universitet, Institutionen för medicin och hälsa, Farmakologi. Linköpings universitet, Hälsouniversitetet.
    Nilsson, Sven E.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oftalmiatrik. Linköpings universitet, Hälsouniversitetet.
    Frennesson, Christina I.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oftalmiatrik. Linköpings universitet, Hälsouniversitetet.
    What does the commonly used DCF test for oxidative stress really show?2010Ingår i: Biochemical Journal, ISSN 0264-6021, E-ISSN 1470-8728, Vol. 428, nr 2, s. 183-90Artikel i tidskrift (Refereegranskat)
    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.

  • 15.
    Kurz, Tino
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Farmakologi. Linköpings universitet, Hälsouniversitetet.
    Karlsson, Markus
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Brunk, Ulf
    Linköpings universitet, Institutionen för medicin och hälsa, Farmakologi. Linköpings universitet, Hälsouniversitetet.
    Erik Nilsson, Sven
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oftalmiatrik. Linköpings universitet, Hälsouniversitetet.
    Frennesson, Christina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oftalmiatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Rekonstruktionscentrum, Ögonkliniken US/LiM.
    ARPE-19 retinal pigment epithelial cells are highly resistant to oxidative stress and exercise strict control over their lysosomal redox-active iron2009Ingår i: AUTOPHAGY, ISSN 1554-8627, Vol. 5, nr 4, s. 494-501Artikel i tidskrift (Refereegranskat)
    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.

  • 16.
    Nilsson, Sven Erik
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Oftalmologi.
    Are there advantages in implanting a yellow IOL to reduce the risk of AMD?2004Ingår i: Acta Ophthalmologica Scandinavica, ISSN 1395-3907, E-ISSN 1600-0420, Vol. 82, nr 2, s. 123-125Artikel i tidskrift (Refereegranskat)
  • 17.
    Nilsson, Sven Erik
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Oftalmologi.
    Bacterial Keratitis and Inflammatory Corneal Reactions: Possible Relations to Contact Lens Oxygen Transmissibility2002Ingår i: CLAO Journal, ISSN 0733-8902, Vol. 28, s. 62-65Artikel i tidskrift (Refereegranskat)
  • 18.
    Nilsson, Sven Erik
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Oftalmologi.
    From basic to clinical research: A journey with the retina, the retinal pigment epithelium, the cornea, age-related macular degeneration and hereditary degenerations, as seen in the rear view mirror2006Ingår i: Acta Ophthalmologica Scandinavica, ISSN 1395-3907, E-ISSN 1600-0420, Vol. 84, nr 4, s. 452-465Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: This Acta Ophthalmologica Award and Gold Medal Honorary Lecture (the Lundsgaard Gold Medal Honorary Lecture) reviews some of the work I have carried out with my mentors and many of my wonderful collaborators and research students over more than 40 years, also including related work by other groups. It concentrates on the basic electrophysiology and ultrastructure of the retina and the retinal pigment epithelium (RPE), as well as covering basic and clinical aspects of the cornea, contact lenses, age-related macular degeneration (AMD) and hereditary diseases. Methods: The review describes research performed using light and electron microscopy, basic and clinical electrophysiology, genetics and biochemistry in animal experiments and in research on patients. It also outlines clinically used techniques, such as laser and photodynamic treatment and scanning laser ophthalmoscopy. Results: The paper reports on the following subjects: the mechanisms behind some of the electrical potentials originating in the retina and the RPE and the use of these potentials in hereditary diseases, corneal receptors for lectins and presumably for bacteria, the turnover of the photoreceptor outer segment and the formation of lipofuscin, including the relation of these processes to AMD, certain treatments for AMD, and hereditary degenerations in animal models, such as the RPE65 gene mutation in Briard dogs, which makes them a model of Leber's congenital amaurosis. The dogs are now treated successfully with gene therapy in the USA, and a clinical trial is in preparation. Conclusion: During the last 40 years we have had the good fortune to experience a dramatic growth in knowledge and understanding within ophthalmic science of basic mechanisms. Huge progress has been made in diagnostics and clinical ophthalmological treatments, much to the benefit of our patients. Even a small contribution made by my group to these developments has been well worth the effort, particularly as scientific work is not just deeply satisfying: it is also fun! © 2006 The Authors Journal compilation © 2006 Acta Ophthalmol Scand.

  • 19.
    Nilsson, Sven Erik
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Oftalmologi.
    Ledare, rapporter från Arvo 20042004Rapport (Övrigt vetenskapligt)
  • 20.
    Nilsson, Sven Erik
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Oftalmologi.
    Medicinska synpunkter på kontaktlinsbärande2001Ingår i: Social rapport. 2001 / [ed] Abdelkebir Khatibi, Linköping: Linköpings universitet , 2001, s. 123-127Kapitel i bok, del av antologi (Övrigt vetenskapligt)
    Abstract [sv]

    Rapporten ger en bred översikt av välfärdsutvecklingen under senare år och av sociala problem bland olika grupper i befolkningen. Arbetslöshet och andra problem på arbetsmarknaden, som försörjningsproblem och fattigdom, missbruk, hemlöshet samt boendesegregation är några av de frågor som behandlas

  • 21.
    Nilsson, Sven Erik
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Oftalmologi.
    Seven-day extended wear and 30-day continuous wear of high oxygen transmissibility soft silicone hydrogel contact lenses: A randomized 1-year study of 504 patients2001Ingår i: CLAO Journal, ISSN 0733-8902, Vol. 27, nr 3, s. 125-136Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: To compare the performance and complication rates of PureVision (Bausch & Lomb, Inc.) high Dk/t silicone hydrogel lenses in 30-day continuous wear and 7-day extended wear. Methods: Five-hundred four (504) patients were randomized to 30-day continuous wear (353 patients) or to 7-day extended wear (151 patients) and followed for 12 months. Results: Eighty percent of patients did not report any symptoms/complaints at the follow-up exams. There were no cases of microbial keratitis. The annual incidence of the four most common clinically significant positive slit lamp findings related to lens wear for the 30-day and the 7-day groups, respectively, were as follows: corneal staining, 10.5% and 10.6%, corneal infiltrates, 4.6% and 2.3%, slight epithelial edema, 2.0% and 3.6%, and tarsal conjunctival abnormalities, 1.6% and 3.0%. There was no significant difference in complication rates between the groups. For reasons related to lens wear, 7.6% in the 30-day group and 13.2% in the 7-day group were dropped from the study. The patients' subjective judgment of comfort, visual quality, freedom from dryness, and lens handling varied from 89 to 95 on a scale of 0 to 100. The success rate was 82.9%, slightly better for the 30-day group (84.4%) than for the 7-day group (79.5%). Conclusion: The complication rate was low. Sight-threatening events, such as bacterial keratitis did not occur. Inflammatory changes were seen, although at a low rate. Anterior segment changes related to hypoxia were minimal. Limbal and bulbar hyperemia decreased significantly after switching patients to PureVision lenses. There was no significant difference in complication rates between the 30-day group and the 7-day group.

  • 22.
    Nilsson, Sven Erik
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oftalmologi.
    Frennesson, Christina
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oftalmologi. Östergötlands Läns Landsting, Rekonstruktionscentrum, Ögonkliniken US.
    Antioxidants and macular degeneration2008Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 105, nr 11, s. 836-836Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

      

  • 23.
    Nilsson, Sven Erik
    et al.
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Oftalmologi. Linköpings universitet, Hälsouniversitetet.
    Sundelin, Staffan
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Oftalmologi. Linköpings universitet, Hälsouniversitetet.
    Wihlmark, Ulf
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Oftalmologi. Linköpings universitet, Hälsouniversitetet.
    Brunk, Ulf
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Patologi. Linköpings universitet, Hälsouniversitetet.
    Aging of cultured retinal pigment epithelial cells: oxidative reactions,lipofuscin formation and blue light damage2003Ingår i: Documenta Ophthalmologica, ISSN 0012-4486, E-ISSN 1573-2622, Vol. 106, nr 1, s. 13-16Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    This report reviews our experimental work on cultured retinal pigment epithelial (RPE) cells, fed native or UV-irradiated photoreceptor outer segments (POS). We showed that significantly more lipofuscin (LF) was formed in cells cultured in 40% oxygen than in cells cultured in 8% oxygen, indicating an involvement of oxidative mechanisms in LF formation. The antioxidants -tocopherol, lycopene, zeaxanthin and lutein significantly reduced LF formation. RPE cells high in melanin content exhibited significantly less formation of LF than cells low in or devoid of melanin, suggesting that melanin acts as an effective antioxidant. The phagocytic capacity of LF-loaded RPE cells was significantly reduced compared to that of unloaded control cells, indicating that LF-loaded RPE cells may be unable to serve the photoreceptors sufficiently regarding phagocytosis of shed outer segment tips. Blue light irradiation destabilized lysosomal membranes in LF-loaded RPE cells and significantly reduced the viability of such cells compared to unloaded, irradiated control cells. These results may be of significance in relation to the development of age-related macular degeneration (AMD).

  • 24.
    Nilsson, Ulla L
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Oftalmologi.
    Frennesson, Christina
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Oftalmologi. Östergötlands Läns Landsting, Rekonstruktionscentrum, Ögonkliniken US/LiM.
    Nilsson, Sven Erik
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Oftalmologi.
    Patients with AMD and a large absolute central scotoma can be trained successfully to use eccentric viewing, as demonstrated in a scanning laser ophthalmoscope2003Ingår i: Vision Research, ISSN 0042-6989, E-ISSN 1878-5646, Vol. 43, nr 16, s. 1777-1787Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Twenty patients with age-related macular degeneration, an absolute central scotoma and a mean visual acuity of 0.04 (20/475) were studied. A scanning laser ophthalmoscope (SLO) was used for microperimetry and determination of preferred retinal locus, often located to the left of the retinal lesion (corresponding to a location to the left of the visual field scotoma), which is considered unfavorable for reading. All 20 patients were trained to use a new and more favorable retinal locus for reading, above (or occasionally below) the retinal lesion (corresponding to a location below or above the visual field scotoma), first by reading scrolled text under simultaneous fixation monitoring and instruction in the SLO and then by reading printed text, using high magnification (mean 14.3╫). For the 18 patients who learned to use eccentric viewing, reading speed with adequate magnification prior to training was 9.0▒5.8 words/min. With training (mean 5.2 hours), it increased significantly (p<0.001) to 68.3▒19.4 words per min. Training of eccentric reading has thus proved to be very successful.

  • 25.
    Sundelin, Staffan P.
    et al.
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Oftalmologi. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Patologi. Linköpings universitet, Hälsouniversitetet.
    Nilsson, Sven Erik
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Oftalmologi. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Patologi. Linköpings universitet, Hälsouniversitetet.
    Lipofuscin-formation in retinal pigment epithelial cells is reduced by antioxidants2001Ingår i: Free Radical Biology & Medicine, ISSN 0891-5849, E-ISSN 1873-4596, Vol. 31, nr 2, s. 217-225Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The accumulation of lipofuscin by retinal pigment epithelium may be an important feature in the pathogenesis of age-related macular degeneration, suggesting the possibility that this common cause of blindness might be prevented or delayed by antioxidants. In support of this idea, we now report significantly reduced formation of lipofuscin when the antioxidant substances lutein, zeaxanthin, lycopene (carotenoids), or α-tocopherol were added to rabbit and bovine (calf) retinal pigment epithelial (RPE) cells exposed to normobaric hyperoxia (40%) and photoreceptor outer segments. Rabbit and calf RPE cells were grown for 2 weeks with addition of one of the test substances every 48 h. The cellular uptake of carotenoids and α-tocopherol was assayed by HPLC after 2 weeks. The lipofuscin-content was measured by static fluorometry (rabbit cells) or by image analysis (calf cells). Both rabbit and calf RPE showed similar results with significantly lower amounts of lipofuscin in antioxidant-treated cells. The effect of carotenoids is especially interesting, since the result is not dependent on their protective effect against photo-oxidative reactions. The chain-breaking abilities of these antioxidants in peroxidative reactions of lipid membranes and quenching of free radicals seem to be of importance for inhibition of lipofuscin formation.

  • 26.
    Sundelin, Staffan P.
    et al.
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Oftalmologi. Linköpings universitet, Hälsouniversitetet.
    Nilsson, Sven Erik G.
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Oftalmologi. Linköpings universitet, Hälsouniversitetet.
    Brunk, Ulf
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Patologi. Linköpings universitet, Hälsouniversitetet.
    Lipofuscin-formation in cultured retinal pigment epithelial cells is related to their melanin content2001Ingår i: Free Radical Biology & Medicine, ISSN 0891-5849, E-ISSN 1873-4596, Vol. 30, nr 1, s. 74-81Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Age-related macular degeneration (AMD), the leading cause of blindness in the developed world, is accompanied by degeneration of the retinal pigment epithelial (RPE) cells. There is an inverse correlation between the melanin content of the eye and the incidence of AMD. Lipofuscin (LF)-accumulation in RPE cells accompanies the process of aging, and may also be related to AMD. This study was designed to evaluate the effect of melanin/melanosomes on the rate of LF formation in cultured rabbit and bovine RPE cells subjected to oxidative stress (40% normobaric O2) and daily supplementation with photoreceptor outer segments for 4 weeks. The LF content was measured at 0, 2, and 4 weeks in RPE cells from pigmented and albino rabbits, as well as in pigment-rich and pigment-poor bovine cells. Albino rabbit and pigment-poor bovine cells accumulated significantly higher amounts of LF than pigmented rabbit cells and pigment-rich bovine RPE cells after both 2 and 4 weeks of exposure. Autometallography of melanin-containing cells, without previous exposure to ammonium sulfide, showed a positive outcome, indicating either the occurrence of pre-existing iron-sulphur clusters or an extremely high intrinsic reducing capacity. These results suggest that melanin acts as an efficient antioxidant, perhaps by interacting with transition metals.

  • 27. Veske, A.
    et al.
    Nilsson, Sven Erik
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Oftalmologi. Östergötlands Läns Landsting, Rekonstruktionscentrum, Ögonkliniken US/LiM.
    Narfström, K
    Gal, A.
    Retinal dystrophy of swedish Briard/Briard-Beagle dogs is due to a 4-bp deletion in RPE65.1999Ingår i: Genomics, ISSN 0888-7543, E-ISSN 1089-8646, Vol. 57, s. 57-61Artikel i tidskrift (Refereegranskat)
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