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  • 1. Andreasson, Sten
    et al.
    Breuer, Debra K
    Eksandh, Louise
    Ponjavic, Vesna
    Frennesson, Christina
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Oftalmologi. Östergötlands Läns Landsting, Rekonstruktionscentrum, Ögonkliniken US.
    Hiriyanna, Suja
    Filippova, Elena
    Yashar, Beverly M
    Swaroop, Anand
    Clinical studies of X-linked retinitis pigmentosa in three Swedish families with newly identified mutations in the RP2 and RPGR-ORF15 genes2003Ingår i: Ophthalmic Genetics, ISSN 1381-6810, E-ISSN 1744-5094, Vol. 24, nr 4, s. 215-223Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: To describe new disease-causing RP2 and RPGR-ORF15 mutations and their corresponding clinical phenotypes in Swedish families with X-linked retinitis pigmentosa (XLRP) and to establish genotype-phenotype correlations by studying the clinical spectrum of disease in families with a known molecular defect. Methods: Seventeen unrelated families with RP and an apparent X-linked pattern of disease inheritance were identified from the Swedish RP registry and screened for mutations in the RP2 and RPGR (for the RP3 disease) genes. These families had been previously screened for the RPGR exons 1-19, and disease-causing mutations were identified in four of them. In the remaining 13 families, we sequenced the RP2 gene and the newly discovered RPGR-ORF exon. Detailed clinical evaluations were then obtained from individuals in the three families with identified mutations. Results: Mutations in RP2 and RPGR-ORF15 were identified in three of the 13 families. Clinical evaluations of affected males and carrier females demonstrated varying degrees of retinal dysfunction and visual handicap, with early onset and severe disease in the families with mutations in the ORF15 exon of the RPGR gene. Conclusions: A total of seven mutations in the RP2 and RPGR genes have been discovered so far in Swedish XLRP families. All affected individuals express a severe form of retinal degeneration with visual handicap early in life, although the degree of retinal dysfunction varies both in hemizygous male patients and in heterozygous carrier females. Retinal disease phenotypes in patients with mutations in the RPGR-ORF15 were more severe than in patients with mutations in RP2 or other regions of the RPGR.

  • 2. Bourghardt Peebo, Beatrice
    et al.
    Peebo, Marcus
    Frennesson, Christina
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Oftalmologi. Östergötlands Läns Landsting, Rekonstruktionscentrum, Ögonkliniken US.
    Relapsing polychondritis: A rare disease with varying symptoms2004Ingår i: Acta Ophthalmologica Scandinavica, ISSN 1395-3907, E-ISSN 1600-0420, Vol. 82, nr 4, s. 472-475Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: Relapsing polychondritis (RPC) is a rare systemic disease affecting primarily cartilaginous and proteoglycan-rich structures. It is a potentially fatal disease with unknown aetiology. There are no specific tests for RPC. The diagnosis is dependant on clinical criteria, which include chondritis of both auricles, non-erosive inflammatory polyarthritis, nasal chondritis, ocular inflammation, respiratory tract chondritis and cochlear and/or vestibular damage. Ocular symptoms will occur in approximately 60% of RPC patients. As an example, a patient with signs of RPC is described. Methods/Result: A 30-year-old woman was referred to our department for evaluation of a central corneal ulcer in the left eye. She had a history of recurrent pain in both her auricles and was also found to have a nasal septum perforation. Relapsing polychondritis was suspected. Conclusion: Non-healing corneal ulcers should alert the ophthalmologist to look for unusual reasons for this condition. RPC is one possible cause.

  • 3. Chong, Victor N H
    et al.
    Keonin, Jason
    Luthert, Phil J
    Frennesson, Christina
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Oftalmologi. Östergötlands Läns Landsting, Rekonstruktionscentrum, Ögonkliniken US.
    Weingeist, David M
    Wolf, Rachel L
    Mullins, Robert F
    Hageman, Gregory S
    Decreased thickness and integrity of the macular elastic layer of Bruch's membrane correspond to the distribution of lesions associated with age-related macular degeneration2005Ingår i: American Journal of Pathology, ISSN 0002-9440, E-ISSN 1525-2191, Vol. 166, nr 1, s. 241-251Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly. In its severest form, choroidal neovessels breach the macular Bruch's membrane, an extracellular matrix compartment comprised of elastin and collagen laminae, and grow into the retina. We sought to determine whether structural properties of the elastic lamina (EL) correspond to the region of the macula that is predilected toward degeneration in AMD. Morphometric assessment of the macular and extramacular regions of 121 human donor eyes, with and without AMD, revealed a statistically significant difference in both the integrity (P < 0.0001) and thickness (P < 0.0001) of the EL between the macular and extramacular regions in donors of all ages. The EL was three to six times thinner and two to five times less abundant in the macula than in the periphery. The integrity of the macular EL was significantly lower in donors with early-stage AMD (P = 0.028), active choroidal neovascularization (P = 0.020), and disciform scars (P = 0.003), as compared to unaffected, age-matched controls. EL thickness was significantly lower only in individuals with disciform scars (P = 0.008). The largest gaps in macular EL integrity were significantly larger in all categories of AMD (each P < 0.0001), as compared to controls. EL integrity, thickness, and gap length in donors with geographic atrophy did not differ from those of controls. These structural properties of the macular EL correspond spatially to the distribution of macular lesions associated with AMD and may help to explain why the macula is more susceptible to degenerative events that occur in this disease.

  • 4.
    Frennesson, Christina
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Oftalmologi. Linköpings universitet, Hälsouniversitetet.
    Age-related maculopathy and macular degeneration: New diagnostic and therapeutic procedures1996Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Age-related maculopathy (ARM) may progress into age-related macular degeneration (AMD), which is often disastrous to near vision and reading. Currently used treatment is generally not successful in a long-term perspective. Therefore, searching for an early detection of functional disturbances as well as for prophylactic treatment appears important.

    Colour contrast sensitivity was measured in patients with soft drusen maculopathy (early ARM). No deterioration in visual function was observed with conventional tests. A highly significant elevation (p<0.001-0.0001) of thresholds for all three colour axes was found, indicating an impairment of retinal function. A tendency towards a bimodal distribution was seen, suggesting a subgroup with a more prominent decrease in foveal sensitivity and possibly at higher risk of progression into the exudative form of the disease. Colour contrast sensitivity appears to be a more sensitive measure of early functional disturbances of the retina than provided by the currently used tests.

    Contrast sensitivity was measured peripheral to an absolute central scotoma in patients with AMD and was found to be significantly lower (p<0.001) than In normals at the same degree of eccentricity. This finding may explain the variations in the need for magnification in low vision patients with identical visual acuity for achieving the same visual performance.

    A new system for evaluating paramacular function and establishing the most suitable area for eccentric viewing was designed. The method facilitates the procedure of teaching and training the patient to use the eccentric viewing technique successfully. Reading speed increased significantly (p<O.OOl) with significantly fewer one-hour training sessions (p<O.OOl) than needed with the current training method.

    In a prospective, randomised study, patients with early ARM were treated with green argon laser photocoagulation perifoveally over the drusen area. Parameters such as visual acuity, colour contrast sensitivity and central visual field were unchanged at the 12-month follow-up. The total drusen area decreased significantly (p<0.0001) after laser photocoagulation over a period of 12 mOnths. No complications were noticed. In a matched control group, the area of drusen tended to increase, and there was a significant difference {p<O.OOl) in drusen area between the two groups after 12 months. In the control group, mean visual acuity (p=0.008) and colour contrast sensitivity along the tritan axis {p=0.044) decreased, and three patients advanced to the exudative stage of AMD during follow-up. The results seem to indicate a promising prophylactic potential of the treatment.

  • 5.
    Frennesson, Christina
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Oftalmologi. Östergötlands Läns Landsting, Rekonstruktionscentrum, Ögonkliniken US.
    Photodynamic therapy with verteporfin in patients with age-related macular degeneration and juxtafoveal choroidal neovascularization2004Ingår i: Acta Ophthalmologica Scandinavica, ISSN 1395-3907, E-ISSN 1600-0420, Vol. 82, nr 6, s. 651-655Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: To investigate the effects of photodynamic therapy (PDT) on juxtafoveal choroidal neovascularization (CNV) in age-related macular degeneration (AMD) in a clinical patient material. Methods: Thirty eyes in 30 consecutive patients with AMD and a juxtafoveal CNV underwent PDT with verteporfin with standard parameters. The patients were followed up for 12 months and retreated every 12 weeks in the event of leakage from CNV. Nineteen patients (63.3%) had a predominantly classic CNV, eight (26.7%) had a 100% occult CNV and three (10%) had a minimally classic lesion. In 27 patients (90%) the lesion was ≤ 3 MPS (Macular Photocoagulation Study) disc diameters and ≤ 3 MPS disc areas. Results: There was a positive correlation between duration of symptoms and loss of visual acuity at 12 months (p < 0.02). For predominantly classic lesions, there was a positive correlation between duration of symptoms and lesion size (p < 0.005). At 12 months, leakage had stopped after 3.3 ± 0.9 treatments in 80% of the patients. Visual acuity remained stable in 63.3% of the patients. Conclusion: Photodynamic therapy appears to be beneficial in patients with AMD and juxtafoveal CNV. Copyright © Acta Ophthalmol Scand 2004.

  • 6.
    Frennesson, Christina
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Oftalmologi. Östergötlands Läns Landsting, Rekonstruktionscentrum, Ögonkliniken US/LiM.
    Prophylactic laser treatment in early age-related maculopathy: An 8-year follow-up in a randomized pilot study shows a reduced incidence of exudative complications2003Ingår i: Acta Ophthalmologica Scandinavica, ISSN 1395-3907, E-ISSN 1600-0420, Vol. 81, nr 5, s. 449-454Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: To study the effect of mild laser treatment on the incidence of exudative complications in patients with soft drusen maculopathy in a longterm perspective. Methods: In a prospective study, 38 patients with early age-related maculopathy and good visual acuity (VA) were randomized either to laser treatment using an argon green laser or to observation. At 8 years, 29 patients remained in the study, 16 in the control group and 13 in the treatment group. Results: During follow-up, mean VA decreased significantly in both groups, to 0.53 in the treatment group (p < 0.05) and to 0.25 in the control group (p < 0.001). At 8 years, 9/16 in the control group showed exudative complications, whereas only 2/13 in the treatment group developed such changes (p < 0.03). Conclusion: In this randomized pilot study, mild laser treatment of soft drusen maculopathy significantly reduced the rate of exudative complications in a longterm perspective. As the study is small, the results should be viewed with caution.

  • 7.
    Frennesson, Christina
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oftalmologi. Östergötlands Läns Landsting, Rekonstruktionscentrum, Ögonkliniken US.
    Ranibizumab--effective, but expensive in macular degeneration2008Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 105, nr 32-33, s. 2161-2161Artikel i tidskrift (Refereegranskat)
    Abstract [en]

      

  • 8.
    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.

  • 9.
    Frennesson, Christina
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oftalmologi. Östergötlands Läns Landsting, Rekonstruktionscentrum, Ögonkliniken US/LiM.
    Larsson, R
    Hultman, Per
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Experimentell patologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk patologi och klinisk genetik.
    Nilsson, SG
    Drusen and choroidal neovascularization (CNV) in patients with dense deposit disease (membrano-proliferative glomerulonephritis type II). Favourable effect of photodynamic treatment (PDT)2003Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 44, s. 1774-Konferensbidrag (Övrigt vetenskapligt)
  • 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.
    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.

  • 11.
    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)
  • 12.
    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.

  • 13.
    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)
  • 14.
    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)
  • 15.
    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.

  • 16.
    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)
  • 17.
    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.

  • 18.
    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.

  • 19.
    Frennesson, Christina
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oftalmologi. Östergötlands Läns Landsting, Rekonstruktionscentrum, Ögonkliniken US/LiM.
    Weingeist, D
    Linkoping Univ, Dept Ophthalmol, Linkoping, Sweden Univ Iowa, Ctr Macular Degenerat, Dept Ophthalmol & Visual Sci, Iowa City, IA USA.
    Nienhaus, H
    Linkoping Univ, Dept Ophthalmol, Linkoping, Sweden Univ Iowa, Ctr Macular Degenerat, Dept Ophthalmol & Visual Sci, Iowa City, IA USA.
    Mullins, RF
    Linkoping Univ, Dept Ophthalmol, Linkoping, Sweden Univ Iowa, Ctr Macular Degenerat, Dept Ophthalmol & Visual Sci, Iowa City, IA USA.
    Hageman, GS
    Linkoping Univ, Dept Ophthalmol, Linkoping, Sweden Univ Iowa, Ctr Macular Degenerat, Dept Ophthalmol & Visual Sci, Iowa City, IA USA.
    Vitronectin distribution in the choroidal stroma and Bruch's membrane as related to age and age-related macular degeneration.2000Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 41, nr 4, s. 120B120-Konferensbidrag (Övrigt vetenskapligt)
  • 20.
    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.

  • 21.
    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.

  • 22.
    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.

  • 23.
    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]

      

  • 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.

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