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1.
  • Abdelkader, Ehab, et al. (author)
  • Analysis of retinal structure and function in cone dystrophy with supernormal rod response
  • 2020
  • In: Documenta Ophthalmologica. - : Springer Science and Business Media LLC. - 0012-4486 .- 1573-2622.
  • Journal article (peer-reviewed)abstract
    • Purpose: To report the clinical and electrophysiological features of cone dystrophy with supernormal rod response (CDSRR). Methods: Retrospective cohort study of 15 unrelated patients (nine males and six females, median age 16, range 5–47 years) diagnosed with CDSRR by clinical examination, full-field electroretinography (ERG) and genetic testing. Observations: History, ophthalmic examination including near vision, color vision and contrast sensitivity assessment, multimodal retinal imaging and ERG. Genetic testing was done for all patients using next-generation sequencing. Results: The rate of consanguinity was 86.7%. Color vision was defective in 56.3%. Near vision was defective in all patients (mean 20/160). Contrast sensitivity was affected in all patients at low contrast of 2.5%. A parafoveal ring of increased autofluorescence imaging was seen in most patients (75%). Supernormal mixed maximal response b-wave was seen bilaterally in 63% of patients (and high normal in 37%). Rod dysfunction with prolonged rod b-wave latency was detected in all. The 30-Hz flicker response was more reduced and delayed compared to the single-flash cone response. A novel homozygous missense variant c.530G>C (p.Cys177Ser) in KCNV2 was detected in one patient, the nonsense homozygous mutation c.427G>T (p.Glu143*) was found in 13 patients, and the nonsense c.159C>G (p.Tyr53*) was found in one patient. Conclusion: This is the largest cohort of CDSRR from a single ethnic background. Rod dysfunction and reduced 30-Hz flicker response were demonstrated in all patients. In contrast to previous descriptions in the literature, a supernormal combined dark-adapted rod-cone ERG was present in the majority of the patients at standard stimulus intensity. Considering the consistent genotype and the demonstration of likely pathogenic genetic variants in all the patients, we argue that the combination of delayed rod b-wave and subnormal flicker response strongly suggests the diagnosis of CDSRR.
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3.
  • Ekesten, Björn (author)
  • Guidelines for clinical electroretinography in the dog: 2012 update
  • 2013
  • In: Documenta Ophthalmologica. - : Springer Science and Business Media LLC. - 0012-4486 .- 1573-2622. ; 127, s. 79-87
  • Journal article (peer-reviewed)abstract
    • The full-field, flash electroretinogram (ERG) is now a widely used test of canine retinal function for the clinical diagnosis of hereditary retinal dystrophies and other causes of retinal degeneration, assessment of retinal function in patients with opaque media, ruling out of generalized retinal diseases in patients with sudden loss of vision and in ophthalmological research, as well as in pharmaceutical and toxicological screening for deleterious side effects of drugs and other chemical compounds. In 2002, the first guidelines for clinical ERGs in this species adopted by the European College of Veterinary Ophthalmologists were published. This work provides an update of these guidelines.
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4.
  • el Azazi, Mildred, et al. (author)
  • Background light adaptation of the retinal neuronal adaptive system. II. Dynamic effects
  • 2004
  • In: Documenta Ophthalmologica. - : Springer Science and Business Media LLC. - 0012-4486 .- 1573-2622. ; 109:2, s. 201-213
  • Journal article (peer-reviewed)abstract
    • The dynamic effects of continuous exposure to light on the neuronal adaptive system of the retina, as indicated by the oscillatory response (OPs) of the electroretinogram (ERG) were studied in the albino rat. Digitally filtered OPs and the a- and b-waves of the corneal ERG were simultaneously recorded in dark adaptation, during continuous light adaptation to four levels of background light (BGL) changing in steps of two log units from 1.43 x 10(-6) cd/m2, referred to as 'low and high scotopic, low and high mesopic' levels. Exposed to 'high scotopic' BGL the total oscillatory response (SOP) significantly enhanced within the first minute, whereas the amplitudes of the a- and b-waves were unaffected. In 'low mesopic' BGL the SOP increased within the first minute, whereas the a- and b-waves significantly decreased. 'High mesopic' BGL instantaneously and profoundly reduced both the SOP and the slow potentials. The individual OPs changed in amplitudes mainly within the first minute of BGL. In general, the earlier OPs (O1 and O2) reacted more to the two 'scotopic' BGL levels, whereas the later OPs (O3 and 04) were more affected by the relatively brighter two 'mesopic' conditions. In conclusion, the rapid increase of the OPs within the first minute of 'high scotopic' and 'low mesopic' BGL exposure may represent a rudimentary light adaptational effect in the rod-dominated rat retina. These findings also suggest that the neuronal adaptive mechanism of the retina seems to be a robust system, probably attaining preservation of visual abilities in the rat on exposure to light.
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6.
  • Gottvall, Eva, et al. (author)
  • Concentration-dependent effects of dopamine on the direct current electroretinogram of pigmented rabbits during prolonged intermittent recording
  • 2003
  • In: Documenta Ophthalmologica. - 0012-4486 .- 1573-2622. ; 106:2, s. 161-169
  • Journal article (peer-reviewed)abstract
    • The direct-current (DC) electroretinogram (ERG) was studied in 24 pigmented rabbits. Four experiments were performed, each including six animals. One eye was injected intravitreally with 0.1 ml dopamine (DA) with an estimated concentration in the vitreous body of 0.0025 mM, 0.025 mM, 0.25 mM and 2.5 mM, respectively. The contralateral eye was injected with the same amount of saline. Following the injection the animals were dark adapted for 30 min and then exposed to repeated light stimuli of low intensity for almost 3 hours (series I: 1 stimulus per 3 min, 10 s duration, light intensity 6.8 x 10(2) lux). After another 30 min period of dark adaptation repeated light stimuli of high intensity were presented to the eyes (series II: 1 stimulus per 70s, 10 s duration, light intensity 6.8 x 10(4) lux) for 33 min. In the control eyes, a slow increase with time of the a-, b-and c-wave amplitudes was observed during series I. During series II, the a- b-and c-wave amplitudes were markedly reduced between the first and the second light stimulus, but subsequently grew to a peak. The behavior of the ERG in the eyes injected with dopamine was not different from that observed in the control eyes at the lowest concentration of the drug. At higher concentrations the b-and c-wave amplitudes were reduced compared with the control eyes, and did not show the slow increase with time observed in these eyes during series I. Peak responses observed during series II in the control eyes was increasingly suppressed in the eyes treated with dopamine. Results of ERG recordings suggest that dopamine influences retinal adaptation in rabbits in a dose dependent manner.
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7.
  • Gottvall, Eva, et al. (author)
  • Long-term behavior and intra-individual stability of the direct current electroretinogram and of the standing potential in the albino rabbit eye
  • 2003
  • In: Documenta Ophthalmologica. - 0012-4486 .- 1573-2622. ; 106:2, s. 195-200
  • Journal article (peer-reviewed)abstract
    • The direct current electroretinogram (ERG) and the standing potential (SP) were studied in seven albino rabbits under general anesthesia. Identical experiments were performed on 2 consecutive days. After 30 min of dark adaptation. repeated light stimuli of maximal intensity of the system were presented to the eyes. The interstimulus interval was 70 s. and stimulus duration 10 s. Each experiment lasted for almost 3 h. In the first experiment, the b- and c-wave amplitudes measured in response to the second light stimulus were markedly reduced compared to those recorded in response to the first stimulus. Both amplitudes then recovered. The b-wave attained a peak about 20 min after the start of light stimulation. The peak was followed by a trough about 20 min later, and the amplitude then slowly increased. Following the minimum recorded during the second light stimulus, the c-wave amplitude reached a peak about 14 min after the start of stimulation. A trough in the amplitude occurred 20 min later. The amplitude then slowly increased to the end value, which was higher than the initial level. The a-wave behaved similarly to the b-wave, but the changes in most cases did not attain statistical significance. A minimum in the SP occurring at the second light stimulus was followed by a peak about 13 min after the start of light stimulation, and then by a trough about 17 min later. In the second experiment, performed one day after the first, the development of the a-. b-, and c-wave amplitudes and of the SP was similar to that observed during the first experiment, and no statistically significant differences between the two experiments were found. The reactions of the ERG and the SP were thus very stable between identical experiments performed on two consecutive days.
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8.
  • Holm, Kristina, et al. (author)
  • In diabetic retinopathy, foveal thickness of 300 mum seems to correlate with functionally significant loss of vision.
  • 2007
  • In: Documenta Ophthalmologica. - : Springer Science and Business Media LLC. - 1573-2622 .- 0012-4486. ; 114:3, s. 117-124
  • Journal article (peer-reviewed)abstract
    • To study the relationship between foveal thickness assessed by optical coherence tomography (OCT) and foveal function measured with multi focal electroretinography (mfERG) in patients with non-proliferative diabetic retinopathy, and with no previous laser treatment. Twenty-six eyes from 18 diabetic patients (13 men), aged 59 years, (range 28-79 years), diabetes duration 15 years, (range 2-27 years), with a macular thickness between 200 and 600 mu m were evaluated by mfERG, visual acuity (ETDRS score) and OCT. Mean amplitudes and implicit times of the mfERG responses were analyzed within the four innermost (14 degrees) of the six concentric rings. For comparison with the results from the OCT (diameter of measured area = 6 mm) we analyzed the summed response from the first and second ring (central zone), corresponding to the central area of the OCT. The third(zone 2) and fourth (zone 3)of the four innermost of the six concentric rings measured by the mfERG corresponding to the second and third area of OCT. An increased macular thickness in the central area of the OCT correlated to reduced amplitudes (r = -0.541; P = 0.004) and prolonged implicit times (r = 0.548; P = 0.004) in the central zone of the mfERG, and inversely correlated with visual acuity, -0.49; P = 0.045. Retinal thickness in the second area was correlated to prolonged implicit times in the second mfERG zone (r = -0.416; P = 0.034). No correlations were found for the third area of the OCT. When macular thickness exceeded 300 mu m the decrease of amplitudes and prolonged implicit times, measured by mfERG, seemed to be more pronounced. In conclusion increased macular thickness is correlated with reduced amplitudes and prolonged implicit times on the mf ERG and worse visual acuity.
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  • Jakobsson, Peter, et al. (author)
  • The effect of spatial frequency and contrast on the latency in the visual evoked potential
  • 1992
  • In: Documenta Ophthalmologica. - 0012-4486 .- 1573-2622. ; 79:2, s. 187-194
  • Journal article (peer-reviewed)abstract
    • The latency in the visual evoked potential was measured at spatial frequencies of 2–12 c/deg in 10 subjects. The contrast levels of the sinuosoidal grating patterns were set at 1.5, 1.75, 2.0, 2.25, 2.5, 2.75 and 3.0 log units above each subject's contrast sensitivity threshold. Two factors were shown to influence the latency: suprathreshold contrast and, to a lesser extent, spatial frequency. The visual evoked potential latencies at contrast sensitivity threshold were extrapolated. These threshold latencies showed considerable variation with spatial frequency and between subjects. Therefore, the visual evoked potential latency cannot be considered a useful tool for estimating the contrast sensitivity function.
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  • Johansson, Björn, et al. (author)
  • Fourier-analysed steadystate VEPs in pre-school children with and without normal binocularity
  • 2006
  • In: Documenta Ophthalmologica. - : Springer Science and Business Media LLC. - 0012-4486 .- 1573-2622. ; 112:1, s. 13-22
  • Journal article (peer-reviewed)abstract
    • Pre-school children aged 4–5 were examined with steady-state VEP in response to a sinusoidal grating pattern with a spatial frequency of 4 c/deg, reversing at rates 5, 10, and 15 Hz. Normal children (n = 10) were compared with subjects lacking stereo perception (n = 6) and with subjects showing significant unilateral amblyopia with visual acuity in the worse eye <0.5 (n = 7). Fast Fourier Transform was used for analysis of the crude steady-state VEP responses. Compared to normals, the subjects lacking stereo perception showed a significantly lower power of the second harmonic in the response evoked by binocular stimulation with gratings reversed at 15 Hz. The amblyopic group showed a significant difference between the dominant and the non-dominant eye regarding the first harmonic power in the responses evoked by gratings reversed at 5 and 10 Hz. These findings are discussed in relation to the magnocellular and parvocellular visual pathways and suggested models for linear and non-linear processing of visual signals.
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13.
  • Johansson, Björn, et al. (author)
  • Fourier analysis of steady-state visual evoked potentials in subjects with normal and defective stereo vision
  • 2000
  • In: Documenta Ophthalmologica. - 0012-4486 .- 1573-2622. ; 101:3, s. 233-246
  • Journal article (peer-reviewed)abstract
    • The purpose of this work was to study the second harmonic in the steady state pattern visual evoked potential (ssVEP) to various stimulus frequencies in subjects with normal and defective binocularity. ssVEPs were elicited by 4 c/deg sinusoidal gratings, with temporal frequencies ranging from 5 to 20 Hz (exp. 1) and 15 to 27.5 Hz (exp. 2). Responses were Fourier analysed and power and phase of the second harmonic to stimulus frequency were measured. For power, binocular enhancement in a bimodal fashion was found both in normals and in subjects with defective binocularity. The power with binocular stimulation was significantly higher in the normal group in the high frequency domain. Latency, estimated from the phase-frequency function, was longer in the group with defective binocularity, but this was statistically significant only for the high frequency domain. The results suggest that a visual system with normal binocular function can follow a stimulus with high temporal frequency more accurately than a system with disturbed binocularity.
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14.
  • Johansson, Björn, 1958- (author)
  • Visual field defect during low-dose methotrexate therapy
  • 1992
  • In: Documenta Ophthalmologica. - : Kluwer Academic Publishers. - 0012-4486 .- 1573-2622. ; 79, s. 91-94
  • Journal article (peer-reviewed)abstract
    • A patient was treated with low-dose methotrexate because of psoriasis that did not respond to conventional therapy. During treatment, visual symptoms occurred; optic disc swelling was found, and later slight optic disc atrophy. Moreover, paracentral relative visual field defects showed fluctuations parallel to methotrexate dose changes. It seems likely that methotrexate affected optic nerve function.
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15.
  • Kjellström, Sten, et al. (author)
  • Retinal function and histopathology in rabbits treated with Topiramate.
  • 2006
  • In: Documenta Ophthalmologica. - : Springer Science and Business Media LLC. - 1573-2622 .- 0012-4486. ; 113:3, s. 179-186
  • Journal article (peer-reviewed)abstract
    • Purpose To evaluate retinal function and histopathology in rabbits treated orally with the antiepileptic drug topiramate. Methods Six rabbits were treated with a daily oral dose of topiramate during a period of eight months. Six rabbits receiving water served as controls. Blood samples were analyzed for determination of topiramate serum levels in order to ensure successful drug exposition. Standardized full-field electroretinograms (ERGs) were performed before treatment and then at 2, 3 and 8 months during the treatment period. After terminating treatment the rabbits were sacrificed and the morphology of the sectioned retina was studied. Results After eight months of treatment the fullfield ERG demonstrated normal rod function in treated and control rabbits, but the light adapted 30 Hz flicker b-wave amplitude was significantly reduced in the treated rabbits. This was the case for both the light adapted (Wilcoxon signed ranks test, P=0.046) and the dark adapted (Wilcoxon signed ranks test, P=0.028) 30 Hz flicker response from the treated rabbits. Retinal immunohistology revealed a severe accumulation of GABA in amacrine cells and in the inner plexiform layer in 4 of 6 treated rabbits compared to the controls. Conclusions Topiramate, orally administrated to rabbits, may cause a significant reduction of the retinal function demonstrated by the reduced b-wave amplitude in the full-field ERG, as well as changes in immunohistology characterized by a severe accumulation of GABA in the inner retina. The retinal dysfunction and the morphological changes indicate that topiramat may damage the retina, similarly to vigabatrin (another antiepileptic drug).
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16.
  • Kjellström, Ulrika, et al. (author)
  • Full-field ERG and visual fields in patients 5 years after discontinuing vigabatrin therapy.
  • 2008
  • In: Documenta Ophthalmologica. - : Springer Science and Business Media LLC. - 1573-2622 .- 0012-4486. ; 117, s. 93-101
  • Journal article (peer-reviewed)abstract
    • Purpose In numerous studies vigabatrin medication has been associated with visual field constriction and alterations in the full-field electroretinogram (ff-ERG), but it is not clear whether these changes are reversible or not. The purpose of this study was to examine patients with visual field loss and reduced ff-ERG several years after discontinuing vigabatrin therapy, in order to investigate reversibility. Methods Eight patients with visual field constriction and reduced cone responses measured by 30 Hz flicker ERG were examined with Goldmann perimetry and ff-ERG 4-6 years after discontinuing medication. The results were compared with investigations conducted during medication, 4-6 years previously. Statistical analysis was also used to compare the ff-ERG results of the patients, during treatment and at follow-up, with a group of 70 healthy subjects. Results Visual field constriction remained 4-6 years after discontinuing vigabatrin therapy. The amplitude of the 30 Hz flicker response also remained reduced on follow-up both compared with the results during treatment and with the control group. Moreover, the amplitude of the isolated rod response and the combined rod-cone response were decreased in the patients compared with the control group, during vigabatrin treatment as well as on follow-up. On follow-up, oscillatory potentials (OPs) also were registered, showing reduced amplitudes in patients compared with controls. The within subject comparison showed no significant changes. Conclusion Vigabatrin attributed visual field constriction and reduced ff-ERG responses remain several years after discontinuing vigabatrin therapy, indicating drug-induced permanent retinal damage.
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  • Magliyah, Moustafa, et al. (author)
  • Late presentation of RPE65 retinopathy in three siblings
  • 2020
  • In: Documenta Ophthalmologica. - : Springer Science and Business Media LLC. - 0012-4486 .- 1573-2622. ; 140:3, s. 289-297
  • Journal article (peer-reviewed)abstract
    • Purpose: Gene therapy for RPE65 retinopathy has been recently approved. The purpose of this study was to assess retinal structure and function in 3 siblings presenting with late-stage RPE65 retinopathy and to assess the unmet need for such therapy in Saudi Arabia. Methods: Search of the retinal dystrophy registry at King Khaled Eye Specialist Hospital and clinical examination including multimodal retinal imaging, full-field electroretinography (ERG), dark adapted full-field stimulus sensitivity thresholds, and molecular genetic testing in 3 patients. Results: Nine (9) patients were identified with biallelic RPE65 mutations, corresponding to a prevalence rate of 9/187 = 5% among early onset retinal dystrophies. Of these, 3 siblings (2 male and 1 female) with RPE65 retinopathy were assessed in detail, because of an unusual, late presentation. They were all over 30 years old at the time of their most recent visits and had non-recordable ERGs. The 2 male siblings presented with poor vision and paracentral loss of the inner segment ellipsoid (ISe) and focal attenuation of the outer nuclear layer (ONL) in the macula. On the other hand, the female sibling presented with 20/100 vision with preserved foveal ISe and intact ONL throughout the macula and significantly lower light sensitivity thresholds compared to her male siblings. A homozygous missense p.Arg91Trp mutation in RPE65 was identified in all. All patients were eligible for gene therapy, demonstrating a central retinal thickness of more than 100 microns on repeated examinations. Conclusions: RPE65 retinopathy seems to be relatively common on the Arabian peninsula, and in addition it may be underdiagnosed. To the best of our knowledge, this is the first detailed presentation, including multimodal retinal imaging and electrophysiological assessment, of such patients from this region. Patients with late presentation of RPE65 retinopathy may be eligible for gene therapy, in terms of remaining retinal function and structural preservation. The therapeutic window of such therapy remains to be determined.
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20.
  • Magliyah, Moustafa S., et al. (author)
  • Evolution of macular hole in enhanced S-cone syndrome
  • 2021
  • In: Documenta Ophthalmologica. - : Springer Science and Business Media LLC. - 0012-4486 .- 1573-2622. ; 142:2, s. 239-245
  • Journal article (peer-reviewed)abstract
    • Purpose: To describe the stages of development and natural course of a full-thickness macular hole (FTMH) in a patient with enhanced S-cone syndrome (ESCS). Methods: This study reported the serial ophthalmologic examinations and macular spectral-domain optical coherence tomography (SD-OCT) imaging over a period of 6 years in a 29-year-old man with ESCS confirmed by electroretinography (ERG) and NR2E3 molecular genetic analysis. Results: At presentation, patient had night blindness and visual acuity (VA) of 20/300 in the right eye (OD) and 20/100 in the left eye (OS). Examination showed bilateral retinal midperipheral pigmentary deposits and a macular schisis in OD. Electroretinography and NR2E3 genetic analysis confirmed ESCS. A year later, a lamellar MH (LMH) appeared at the fovea in OD. SD-OCT confirmed it as inner retinal layer LMH with outer retinal preservation and displayed, on the temporal side of the LMH, prominent splitting between the inner and outer retinal layers. At 2 years, a focal defect in the ellipsoid zone appeared on SD-OCT, followed by split in the outer retinal layer creating a progressively expanding outer LMH. The latter had rolled edges which then fused with the inner LMH margins creating a single full-thickness FTMH. Over the next 4 years, enlargement of the FTMH with increased adjacent retinal splitting continued. No visible vitreous abnormalities or vitreoretinal traction forces were identified at any stage during follow-up. VA OD remained unchanged. Conclusion: This case illustrates that the clinical evolution of FTMH in ESCS may be progressive and likely involves degeneration and intraretinal, rather than vitreoretinal, traction. This should be kept in mind when considering surgical intervention in these cases.
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21.
  • Molnar, Anna E. C., et al. (author)
  • Macular function measured by binocular mfERG and compared with macular structure in healthy children
  • 2015
  • In: Documenta Ophthalmologica. - : Springer Science and Business Media LLC. - 0012-4486 .- 1573-2622. ; 131:3, s. 169-176
  • Journal article (peer-reviewed)abstract
    • To create normative data in children from binocular multifocal ERG (mfERG) recordings and compare results with the macular thickness. Forty-nine 5- to 15-year-old healthy, full-term children were examined with Espion Multifocal System, using DTL electrodes. The stimulus matrix consisted of 37 hexagonal elements. Amplitudes, implicit times and response densities (presented in three rings) of the first-order component P1 were analyzed. Measurements of macular thickness were performed with spectral-domain Cirrus OCT. There were no significant differences between right and left eyes regarding mfERG recordings. Median P1 implicit times of Rings 1-3 of the 46 right eyes were 30.0, 30.0 and 30.8 ms and response densities 20.5, 10.9 and 7.6 nV/deg(2), respectively. Implicit time was longer in boys than in girls (p = 0.009, 0.039, 0.005 in Rings 1-3) and was correlated with age (r (s) = 0.417, 0.316, 0.274 in Rings 1-3). Implicit time in Ring 1 correlated significantly with the inner circle of the OCT measurements (p = 0.014). Binocular mfERG with DTL electrodes is a reliable test of the central macular function in children and correlates with macular structure. As previously not shown, there was a significant difference in implicit time between boys and girls.
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  • Nilsson, Sven Erik, 1931-, et al. (author)
  • Aging of cultured retinal pigment epithelial cells : oxidative reactions,lipofuscin formation and blue light damage
  • 2003
  • In: Documenta Ophthalmologica. - 0012-4486 .- 1573-2622. ; 106:1, s. 13-16
  • Journal article (peer-reviewed)abstract
    • 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).
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  • Ponjavic, Vesna, et al. (author)
  • Alterations in electroretinograms and retinal morphology in rabbits treated with vigabatrin
  • 2004
  • In: Documenta Ophthalmologica. - 1573-2622. ; 108:2, s. 125-133
  • Journal article (peer-reviewed)abstract
    • PURPOSE: To determine whether long-term treatment with the anti-epileptic drug vigabatrin causes damage to rabbit retina.METHODS: Five rabbits were treated continuously with a daily dose of vigabatrin solution per orally during a period of 1-8 months. Two rabbits receiving water were used as controls. Repeated full-field electroretinograms (every two weeks) were assessed during this period. Vigabatrin serum concentration was repeatedly measured for securing successful drug administration. After termination of treatment the rabbits were sacrificed and the morphology of the sectioned retina was studied.RESULTS: In all rabbits treated with vigabatrin the serum analyses repeatedly demonstrated elevated drug concentration. Full-field electroretinograms demonstrated normal rod function in all treated rabbits, but reduced cone function in two of the five treated rabbits verified by 30Hz flicker stimulation. Morphologic studies of the sectioned retina demonstrated GFAP immunoactivity of the glial cells localized in the retinal periphery in all five treated rabbits, one of which had staining also in the centrally localized glial cells. The treated rabbits also demonstrated a weaker GAD staining in the IPL and less positive amacrine cells, compared to the controls. Only two treated rabbits had normal GABA staining while three had an enhanced GABA immunoreactivity and undistinguishable fibers in the IPL. In three out of five treated rabbits the Müller cells were short, stubby and fragmented, with swollen endfeet.CONCLUSION: This study demonstrates changes in histopathology caused by vigabatrin in an animal model, which has not been reported previously. We have found that vigabatrin orally administrated to rabbits does not affect rod function but may reduce cone function in the full-field electroretinogram, which is similar to the previously reported vigabatrin effect on the human ERG. The results indicate that vigabatrin may damage or influence, at least one cell type in the rabbit retina.
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24.
  • Schroeder, Marion, et al. (author)
  • Electrophysiological evaluation and 18-month follow-up of two regimens with aflibercept for neovascular age-related macular degeneration
  • 2022
  • In: Documenta Ophthalmologica. - : Springer Science and Business Media LLC. - 1573-2622 .- 0012-4486. ; 144:2, s. 99-115
  • Journal article (peer-reviewed)abstract
    • PURPOSE: To compare two aflibercept treatment regimens and the electrophysiological outcome concerning cone and rod function in age-related macular degeneration (nAMD) over 18 months.METHODS: 41 patients with treatment-naïve nAMD were randomized 1:1 to either arm 1 or 2. Arm 1 received three consecutive monthly aflibercept injections, followed by bimonthly treatment until week 52. Thereafter, a treat-and-extend (TAE) regimen was applied. Arm 2 was treated according to a TAE protocol throughout the 18-month follow-up. We assessed visual acuity (VA), central retinal thickness (CRT), injection rate and interval, and evaluated cone and rod function with full-field and multifocal electroretinography (ffERG, mERG).RESULTS: There were no statistically significant differences in mean baseline VA, lesion type, age, gender, or symptom duration between the two arms. During the 18-month follow-up, mean VA improved in arm 1 (n = 19) from 63.5 ± 10.5 to 69.1 ± 9.2 letters; p = 0.098; and in arm 2 (n = 20) from 66.8 ± 13.6 to 73.9 ± 9.0 letters; p = .002. In both arms, mean CRT was significantly reduced; p < 0.000. At month 18, we found no significant difference in the number of injections or injection intervals between groups. Arm 1 had received 11.3 ± 1.7 injections vs. 10.9 ± 2.0 in arm 2. The mean injection interval was 9.2 ± 3.4 weeks vs. 9.5 ± 3.1, with 52% (n = 10) on the maximum 12-week interval in arm 1, and 50% (n = 10) in arm 2. The combined rod-cone a-wave amplitude significantly decreased over time; p = 0.043. The isolated rod b-wave amplitude showed a statistically significant decline; p = 0.026. The overall mERG amplitude and implicit time remained unchanged over time; p = 0.878 vs. p = 0.922. The central ring 1 mERG amplitude improved; p = 0.041, with an unaffected implicit time.CONCLUSIONS: After 18 months, both treatments arms have received a similar number of injections at comparable intervals. Electrophysiological evaluation shows no signs of toxicity concerning cone function. But ffERGs for the combined and isolated rod response have declined, possibly reflecting either toxic effects of the drug to rods or the natural course of the disease itself.
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25.
  • Sterner, Bertil, et al. (author)
  • Accommodative facility training with a long term follow up in a sample of school aged children showing accommodative dysfunction
  • 1999
  • In: Documenta Ophthalmologica. - : Springer. - 0012-4486 .- 1573-2622. ; 99:1, s. 93-101
  • Journal article (peer-reviewed)abstract
    • The primary aim of this project was to study the effect of flip lens-training on the accommodative function in a group of children with accommodative dysfunction and subjective symptoms such as asthenopia, headache, blurred vision, and avoidance of near activity. We also wanted to measure the accommodative facility among the children in comparison with a control group. Another aim of the study was whether flip lens-training increased accommodative facility, and to find out if it also had a positive effect on their asthenopia and related problems also in long term. Following the training period the accommodative facility and accommodative function significantly increased and two years after finishing the training period no child had regained any subjective symptoms and the objective findings were almost the same as at the end of facility training period. These results suggest that accommodative facility training is an efficient method built on loss of symptoms among children with accommodative infacility.
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26.
  • Tyrberg, Maria, et al. (author)
  • Electrophysiological studies in newly onset type 2 diabetes without visible vascular retinopathy
  • 2011
  • In: Documenta Ophthalmologica. - : Springer Science and Business Media LLC. - 0012-4486 .- 1573-2622. ; 123:3, s. 193-98
  • Journal article (peer-reviewed)abstract
    • The purpose of this study was to investigate the early alterations of retinal function, assessed with electrophysiology, in newly onset type 2 diabetes patients without vascular retinopathy. Seventeen patients with newly diagnosed type 2 diabetes (duration 7 ± 3 months), without any vascular retinopathy in fundus photographs, were examined with full-field electroretinogram (ERG) and multifocal ERG (mfERG). The results were compared with those of age-matched subjects without diabetes. In the dark-adapted full-field ERG, the a-wave and the 30-Hz flicker implicit times were delayed in diabetes patients compared to controls, P = 0.001 and P = 0.020. In the first-order kernel of the mfERG, the first positive wave, P1, was delayed in all areas measured. The electrophysiological examinations demonstrate early alterations of retinal function characterised by a delayed a-wave implicit time in the darkadapted full-field ERG, representing the rod signalling, and alterations in the multifocal ERG reflecting cone and/or postreceptoral function.
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27.
  • Tyrberg, Maria, et al. (author)
  • Multifocal electroretinogram (mfERG) in patients with diabetes mellitus and an enlarged foveal avascular zone (FAZ)
  • 2008
  • In: Documenta Ophthalmologica. - : Springer Science and Business Media LLC. - 1573-2622 .- 0012-4486. ; 117, s. 185-189
  • Journal article (peer-reviewed)abstract
    • Purpose To assess the relationship between foveal microcirculation and central retinal function in diabetic patients having both an enlarged foveal avascular zone (FAZ) and a preserved visual acuity (0.6 or better). Methods Twenty-five patients with diabetes type 1 or 2 with an enlarged FAZ (largest diameter > 650 mum) measured in fluorescein angiograms were examined with multifocal ERG (mfERG). The largest FAZ diameter, the FAZ area as well as the adjacent perifoveal intercapillary area (PIA), was calculated from the fluorescein angiogram. The retinopathy level was mild to preproliferative. There was no macular edema and no eye had previously been treated with photocoagulation. Results The mean FAZ diameter was 0.92 +/- 0.17 mm and the mean summed area (FAZ and PIA) was 0.74 +/- 0.24 mm(2). There was a significant correlation between increasing FAZ diameter and increasing implicit time of the innermost concentric rings and of the third concentric ring in the first order kernel of the mfERG (P = 0.03 and P = 0.008, respectively). An increasing summed area (FAZ and PIA) was correlated to increasing implicit time in the same areas of the mfERG (P = 0.005 and P = 0.026, respectively). No correlation was seen between the ischemic areas and the mfERG amplitudes. Conclusion A correlation between the ischemic areas and prolonged implicit time in the mfERG indicates that alterations in neuronal macular function due to ischemia might precede the deterioration of visual acuity.
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28.
  • Tyrberg, Maria, et al. (author)
  • Multifocal electroretinography (mfERG) in insulin dependent diabetics with and without clinically apparent retinopathy
  • 2005
  • In: Documenta Ophthalmologica. - : Springer Science and Business Media LLC. - 1573-2622 .- 0012-4486. ; 110:2-3, s. 137-143
  • Journal article (peer-reviewed)abstract
    • Purpose: To Study the retinal function, using multifocal electroretinography (mfERG), in diabetic patients with mild and moderate retinopathy, and in diabetics without clinically apparent retinopathy. Methods: Thirty-one patients with insulin dependent diabetes mellitus, eleven without any clinically apparent retinopathy, twelve with mild retinopathy and eight with moderate retinopathy, were studied. Ophthalmologic examination included testing Of Visual acuity, fundus inspection, fundus photography and mfERG. Sixteen subjects without eye disease and with normal visual acuity were used as controls for comparison of mfERG results. Results: The patients had a mean diabetes duration of 23 +/- 9 years. All patients and controls had a visual acuity of 1.0. In the first order component of the mfERG there were significantly higher ring amplitudes in the diabetics compared to the controls (p=0.001). In the second-order component of the mfERG, there was a significantly prolonged implicit time in the diabetics who had retinopathy compared to those without any retinopathy (p=0.026). The third positive waveform in the ring amplitudes of the second-order component, were absent in 15/31 of patients with diabetes, but were easily distinguished in all the controls; p < 0.001. This waveform was absent in 6/11 patients without retinopathy. Conclusion: Patients with insulin dependent diabetes have specific abnormalities in both the First and the second-order component of the mfERG. These abnormalities reflect both vascular changes in the retina and, probably simultaneously, pathology in inner retinal function, also in the diabetics without clinically apparent retinopathy.
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29.
  • Wang, L, et al. (author)
  • Background light adaptation of the retinal neuronal adaptive system. I. Effect of background light intensity.
  • 2001
  • In: Documenta Ophthalmologica. - 0012-4486 .- 1573-2622. ; 103:1, s. 13-26
  • Journal article (peer-reviewed)abstract
    • The behaviour of the neuronal adaptive retinal mechanisms to environmental light exposures was studied by measuring the oscillatory potentials (OPs) of the electroretinogram. Dark adapted rats were exposed to four levels of background light (BG), starting at a 'low scotopic' level of 1.43x 10(6) cd/m2, increased by steps of two log units, through 'high scotopic' -, 'low mesopic' - and finally the 'high mesopic' BG of 1.43x 10(0) cd/m2. The summed oscillatory response significantly increased as the BG intensity was raised, except at the 'high mesopic' level. The amplitudes of the a- and b-waves reduced as the BG light increased above the 'high scotopic' level. Each OP responded individually to the different BGs. O1 and O2, significantly enhanced at the 'low scotopic' BG. The amplitudes of the three later OPs increased significantly at the 'low mesopic' BG. The adaptational behaviour of the retinal oscillatory response to BG illumination was different to that of the a- and b- waves. The results indicate that the adaptational neuronal system, as reflected by the OPs, seems to be relatively robust and is separate from the slower photochemical adaptive process in the distal retina. The tentative corollary suggests the oscillatory system to play a vision-preserving role, possibly as an alert against undue depletion of the slowly regenerating visual pigment. The enhancement of the oscillatory response at the 'mesopic' illumination levels indicate both scotopic and photopic processes to contribute to neuronal adaptive activity of the retina.
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30.
  • Wright, Tom, 1973, et al. (author)
  • A comparison of signal detection techniques in the multifocal electroretinogram.
  • 2008
  • In: Documenta ophthalmologica. Advances in ophthalmology. - : Springer Science and Business Media LLC. - 0012-4486. ; 117:2, s. 163-70
  • Journal article (peer-reviewed)abstract
    • A common task in the analysis of the multifocal electroretinogram (mfERG) is determining which retinal areas have preserved signal in recordings which are attenuated by the effects of disease. Several automated methods have been proposed for signal detection from multifocal recordings, but no systematic study has been published comparing the performance of each. This article compares the sensitivity and specificity of expert human scoring with three different automated methods of mfERG signal detection. Recordings from control subjects were artificially modified to simulate decrease in signal amplitudes (attenuation) as well as total signal loss. Human scorers were able to identify areas with preserved signal at both low and high attenuation levels with a high specificity (minimum 0.99), sensitivities ranged from 0.2 to 0.94. Automated methods based on template correlation performed better than chance at all attenuation levels, with a slide fit method having the best performance. Signal detection based on signal to noise ratio performed poorly. In conclusion automated methods of signal detection can be used to increase signal detection sensitivity in the mfERG.
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31.
  • Wright, Tom, 1973, et al. (author)
  • Analysis of multifocal electroretinograms from a population with type 1 diabetes using partial least squares reveals spatial and temporal distribution of changes to retinal function.
  • 2012
  • In: Documenta ophthalmologica. Advances in ophthalmology. - : Springer Science and Business Media LLC. - 1573-2622. ; 125:1, s. 31-42
  • Journal article (peer-reviewed)abstract
    • Spatial-temporal partial least squares (ST-PLS) is a multivariate statistical analysis that has improved the analysis of modern imaging techniques. Multifocal electroretinograms (mfERGs) contain a large amount of data, and averaging and grouping have been used to reduce the amount of data to levels that can be handled using traditional statistical methods. In contrast, using all acquired data points, ST-PLS enables statistically rigorous testing of changes in waveform shape and in the distributed signal related to retinal function. We hypothesise that ST-PLS will improve analysis of the mfERG. Two mfERG protocols, a 103 hexagon clinical protocol and a slow-flash mfERG (sf-mfERG) protocol, were recorded from an adolescent population with type 1 diabetes and an age similar control population. The standard mfERGs were analysed using a template-fitting algorithm and the sf-mfERG using a signal-to-noise measure. The results of these traditional analysis techniques are compared with those of the ST-PLS analysis. Traditional analysis of the mfERG recordings revealed changes between groups for implicit time but not amplitude; however, the spatial location of these changes could not be identified. In contrast, ST-PLS detected significant changes between groups and displayed the spatial location of these changes on the retinal map and the temporal location within the mfERG waveforms. ST-PLS confirmed that changes to diabetic retinal function occur before the onset of clinical pathology. In addition, it revealed two distinct patterns of change depending on whether the multifocal paradigm was optimised to target outer retinal function (photoreceptors) or middle/inner retinal function (collector cells).
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32.
  • Åkerblom, Hanna, et al. (author)
  • Macular function in preterm children at school age
  • 2016
  • In: Documenta Ophthalmologica. - : Springer Science and Business Media LLC. - 0012-4486 .- 1573-2622. ; 133:3, s. 151-157
  • Journal article (peer-reviewed)abstract
    • Macular development is a complex process that starts by mid-gestation and continues several years after birth. A preterm birth could affect this development, causing increased thickness in the central macula, but the effect of the macular function remains uncertain. The aim of this study was to investigate the macular function measured with multifocal electroretinography (mfERG), in former preterm children and compare with healthy controls. A second aim was to correlate central macular function with central macular thickness measured with optical coherent tomography (OCT), in the preterm group. Fifteen former preterm children born before 32 weeks of gestation were included in the study. MfERG results from 12 children acted as controls. Visual acuity, refraction in cycloplegia and mfERG were carried out in all children, and optical coherent tomography (OCT) was performed in the preterm children. Main outcomes were P1 amplitudes and implicit times for Rings 1-5 and "sum of groups" of the mfERG, and central macula thickness in area A1 measured with OCT. The P1 amplitudes were reduced in Rings 1-5 and "Sum of groups" in the preterm children compared to controls. There were no significant correlation between P1 amplitude or implicit times in Ring 1 and central macular thickness in the preterm group. Macular function is reduced in former preterm children compared to children born at term. This suggests that the structural changes with a thicker central retina can have an effect on function and may be one, of probably several, explanations for visual dysfunction in preterm children at school age.
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