No / Department of Health

Age-related maculopathy (ARM) is a central retinal disease with unclear pathogenesis. It is the major cause of permanent vision loss in adults over 50 years and is increasing in prevalence and incidence, faster than the aging population would suggest. Early in the disease process (early ARM) there is little or no vision loss and there are only slight retinal changes with abnormal deposits within Bruch's membrane. As the disease progresses (late ARM or age-related macular degeneration, AMD) vision loss may be quite severe due to atrophy (dry AMD) or the development of chorioretinal neovascularisation (CNV, wet AMD). It is hard to predict from conventional eye examinations and clinical vision tests which cases will progress to the severe, dry or wet forms of the disease. Moreover, most of the conventional clinical tests are based upon subjective vision measures. Objective tests which detect ARM earlier would be a useful aid to diagnosis and to monitoring progression. The multifocal electroretinogram (mfERG) is a relatively new clinical tool which enables the recording of electrical potentials from multiple, small areas of the central retina and thus assesses function from specific retinal locations. It is therefore useful in detecting focal retinal diseases such as hereditary or acquired maculopathies or in monitoring retinal laser or surgical treatment effects. There is cone and rod impairment in ARM and histopathological and psychophysical evidence for a preferential vulnerability of rods compared to cones. This research project investigated if an objective tool such as the mfERG could detect early ARM,its progression and the treatment effects of multiple photodynamic therapies (PDT) on retinal function in late ARM, prior to a battery of subjective vision measures. For comparison purposes a subjective assessment of central retinal function was performed using high and low contrast distance visual acuities (VA), near VA, low luminance VA (SKILL cards), contrast sensitivity (Pelli-Robson, P-R), saturated and desaturated Panel D-15 (sat Panel D-15, desat Panel D-15) and central visual fields (Humphrey 10-2, mean sensitivity, MS and mean defects, MD). As an objective assessment of central retinal function the cone- and rod-mediated multifocal electroretinograms were recorded. Subjective and objective tests of retinal function were compared in early ARM and an age-matched control group (chapter 3). Seventeen eyes of seventeen subjects with early ARM and twenty control subjects with normal vision were measured. For the cone-mediated mfERG responses conventional averaging methods were used and results were correlated with subjective vision tests. The conventional cone-mediated mfERG failed to distinguish between the early ARM and control subjects whereas subjective vision measures such as HC- and LC-VA, desat Panel D-15, MS, P-R were significantly reduced in the ARM group. However, there were significant correlations between the cone-mediated mfERG and the desat Panel D-15 results in the ARM group. This suggests that the mfERG measures similar retinal processes that detect colour vision deficiency under desaturated conditions. There was no significant correlation between cone-mediated mfERG measures and funduscopic changes. The conclusion from this study was that the subjective vision tests detected early ARM better than the objective cone-mediated mfERG. Thus the aim of detecting early ARM objectively was not met by the cone-mediated mfERG suggesting the need to develop other objective tests such as a rod-mediated mfERG. Whether the preferential rod vulnerability others have reported in early ARM could be detected by the rod-mediated mfERG was determined in the next study (chapter 4). A protocol for recording rod-mediated mfERG responses was developed by determining the optimal testing luminance to reduce the effect of stray light and elicit maximal rod-mediated responses. Sixteen of the seventeen ARM subjects and seventeen control subjects from the previous study were tested. For analysis, a customized computer template fitting method was developed in MATLAB (Mathworks, Natick, MA, USA). This method has been shown to be useful for low signal-to-noise ratio responses that characterize the rod-mediated mfERG. Significantly delayed rod-mediated mfERG responses were found whereas cone-mediated mfERG responses were within the normal range. This suggested that the effect of ARM on the rod system could be detected objectively with the rod-mediated mfERG before changes in the cone-mediated mfERG. Which of the tests best detected progression of vision loss was investigated in chapter 5. Visual function of 26 (13 ARM and 13 control subjects) of the original 37 subjects (17 ARM and 20 control subjects) had cone- and rod-mediated mfERG and the subjective vision measures repeated after one year. The main purpose was to determine which of the tests best detected progression of vision loss. The mfERG results were analysed by using both averaged and local responses and by using the computer template fitting procedure. On average no significant worsening of either objective or subjective function measures was evident after one year. These results reinforce the slow progression of the disease. With a longer follow-up period progression of ARM may translate into measurable changes in the mfERG and the other visual function tests. The effect of multiple photodynamic therapies (PDT) on cone- and rod-mediated function was assessed with the mfERG in the last study (chapter 6). The cumulative treatment effects of PDT in five subjects with late ARM were determined. Having demonstrated that the rod-mediated mfERG was applicable in early ARM, this study also aimed to investigate how useful it was in late ARM where there is substantially greater rod loss. Cone- and rod-mediated mfERGs, visual acuities, contrast sensitivities and central visual fields were investigated a week before treatment began and then one month after each PDT treatment. The subjects received three treatments each over an average period of five and a half months. In some subjects there were significant transient reductions in cone- and rod-mediated amplitudes possibly reflecting alterations in choroidal hypoperfusion dynamics one month after treatment. Further, b-wave component of the mfERG became increasingly misshapen after each PDT treatment suggesting an ischemic insult mainly targeting post-receptoral sites. However, objective and subjective function was stabilized after multiple PDT treatments in most of the subjects. This pilot study of five cases showed that there was no additional damage to cone- and rod-mediated outer retinal function after three PDT treatments. One of the novel findings of this research was that the rod-mediated function measured with the mfERG was impaired in early ARM. This finding supports histopathological and psychophysical evidence of rod vulnerability in early ARM. The results of these studies also suggest that early ARM affects different aspects of visual function which is reflected by different outcomes from objective and subjective vision tests. A model (chapter 7) based upon the results was developed proposing a hypoxic insult with a preferential alteration of post-receptoral sites in early ARM. The cone-mediated mfERG documented the retinal damage and possible treatment effects on outer retinal function of the multiple PDTs which did not further deteriorate. Thus, this technique might assist in the development of optimal treatment modalities for ARM, especially in retreatment regimes. Greater variability was found for the rod-mediated mfERG and its clinical use in PDT treatment regimes still needs to be investigated. In conclusion, this research has provided a better understanding of the disease process and treatment effects in ARM and might contribute to improvements in diagnosis and treatment of ARM.

Background: Optical coherence tomography (OCT), multifocal electroretinography (mfERG) and full-field electroretinography (ffERG) give important information about retinal structure and function. Purpose: To collect normative data of macular Cirrus Spectral domain (SD)-OCT assessments and of mfERG measurements of healthy children (papers I and II). To assess the macular thickness with Cirrus SD-OCT and the retinal function with ffERG in 6.5-year-old children born extremely preterm and in children born at term (papers III and IV). Methods: Study participants aged 5-15 years and living in Uppsala County were randomly chosen from the Swedish Birth Register (papers I and II). In papers III and IV, the study participants consisted of children born extremely preterm and children born at term – all were aged 6.5 years. In paper III, the children were living in Stockholm and Uppsala health care regions and, in paper IV, in Uppsala health care region only. Macular thickness was assessed with Cirrus SD-OCT and macular function with mfERG, using the Espion Multifocal system and DTL-electrodes. The retinal function was assessed with ffERG and DTL-electrodes, using the Espion Ganzfield system. Results: Altogether, 58 children participated in paper I and 49 children in paper II. In paper I, the repeatability and reproducibility of the OCT assessments were good. In paper II, the results of the mfERG measurements were in accordance with retinal cone density and there were no significant differences between the right and left eyes. In paper III, 134 preterm children and 145 children born at term constituted the study population. The central macular thickness was significantly thicker in the preterm group than in the control group. Within the preterm group, gestational age (GA), former retinopathy of prematurity (ROP) and male gender were all important risk factors for an increased macular thickness. In paper IV, 52 preterm children and 45 control children constituted the study population. Significantly lower amplitudes and prolonged implicit times of the combined rod and cone responses, as well as of the isolated cone responses, were found in the preterm group when compared with the control group. In paper IV, there was no association between GA, ROP or male gender and the ffERG assessments. Conclusion: Normative data of Cirrus SD-OCT and mfERG assessments were reported. The results of the assessments were reliable. Children aged 6.5 years, born extremely preterm, had a significantly thicker central macula and both rod and cone function were significantly reduced in comparison to children born at term. ROP had an influence on retinal structure but not retinal function in the present cohorts. Our results suggest that retinal development is abnormal in children born extremely preterm. Long-term follow-up studies are necessary in order to evaluate the functional ophthalmological outcome in this vulnerable population of children growing up today.

Objetivos: Avaliar a função e estrutura da retina de pacientes com membrana epirretiniana (MER) ou buraco macular (BM) antes e após a cirurgia, e determinar suas relações e os valores preditivos para a acuidade visual após tratamento com vitrectomia associada a peeling da membrana limitante interna. Casuística e Métodos: Foram incluídos 51 olhos de 50 pacientes com indicação de tratamento cirúrgico de MER ou BM idiopáticos. Foi realizada avaliação oftalmológica completa, incluindo melhor acuidade visual corrigida (MAVC) no pré-operatório e nas semanas 1, 3, 8, 24 e 48 após a cirurgia, enquanto que eletrorretinografia multifocal (mfERG) e tomografia de coerência óptica (OCT) foram realizadas antes da cirurgia e dois e doze meses após o procedimento. Os resultados da mfERG serão apresentados na forma da razão entre os valores encontrados nos dois anéis centrais, normalizados pelas médias dos três anéis periféricos (denominada razão P1), para minimizar a variabilidade interpessoal desse teste e ressaltar as alterações encontradas nos anéis centrais. A OCT foi usada para calcular o quociente entre medidas da altura e base do BM (IBM). Resultados: Quarenta e cinco pacientes (46 olhos; n = 30 BM e 16 MER) completaram as 48 semanas de seguimento. No pré-operatório, a média ± SE da MAVC (logMAR) para os grupos BM e MER, respectivamente, foi: 0,93 ± 0,22 (20/170; ou 0,12 decimal) e 0,58 ± 0,11 (20/76; ou 0,26 decimal), com melhora significativa após 48 semanas de seguimento (média ± EP da diferença entre as acuidades visuais medidas em logMAR em 48 semanas e a basal) -0,25 ± 0,07 para o grupo BM e -0,29 ± 0,06 para o grupo MER. O mfERG mostrou-se alterado antes da cirurgia para BM, com melhora da razão P1 após a cirurgia. Para o BM, houve correlação entre a razão P1 no pré-operatório e o ganho da MAVC na semana 8 após a cirurgia (r = -0,42; p = 0,033), mas essa correlação não foi observada para o grupo MER. Também não houve correlação entre o IBM e a acuidade visual após a cirurgia. Conclusões: Os resultados indicam que pacientes com BM apresentando mfERG com baixa razão P1 têm menor probabilidade de ganho de visão após a cirurgia, mas essa afirmativa não é válida para a MER. / Purpose: To evaluate retinal structure and function in eyes with macular hole (MH) or epiretinal membrane (ERM) before and after pars-plana vitrectomy with internal limitant membrane (ILM) peeling, to determine function/structural interrelations and predictive values of postoperative visual acuity. Casuistic and Methods: Fifty-one eyes of 50 patients with idiopathic MH or ERM were included. Comprehensive ophthalmologic evaluation including best-corrected visual acuity (BCVA) was performe date baseline, 1, 3, 8, 24 e 48 weeks after surgery, while optical coherence tomography (OCT) and multifocal ERG was performed before and at 2 and 12 months after surgery. mfERG results are show using the ratio between the amplitude averages of the 2 central rings and the 3 peripheral rings (P1 ratio) and OCT was used to calculate the macular hole index (MHI) defined by the quotient between hole height/base. Results: Forty-five patients (46 eyes; n = 30 MH and 16 ERM) finished follow-up. Mean ± SE (logMAR) preoperative BCVA was 0.93 ± 0.22 and 0.58 ± 0.11 for MH and ERM respectively, and improved in -0.25 ± 0.07 logMAR for MH and -0.29 ± 0.06 logMAR for ERM. mfERG P1 ratio was reduced in BM, and increased significantly after surgery. There was significant correlation between preoperative P1 ratio and BCVA gainat week 8 for MH group (r = -0,42; p = 0,033), but not for ERM group. There was no correlation between preoperative MHI and postoperative BCVA. Conclusion: This data indicates that patients with MH and poor mfERG amplitudes have worse prognoses for BCVA improvement, but does not apply for ERM.

Objetivos: Avaliar a função e estrutura da retina de pacientes com membrana epirretiniana (MER) ou buraco macular (BM) antes e após a cirurgia, e determinar suas relações e os valores preditivos para a acuidade visual após tratamento com vitrectomia associada a peeling da membrana limitante interna. Casuística e Métodos: Foram incluídos 51 olhos de 50 pacientes com indicação de tratamento cirúrgico de MER ou BM idiopáticos. Foi realizada avaliação oftalmológica completa, incluindo melhor acuidade visual corrigida (MAVC) no pré-operatório e nas semanas 1, 3, 8, 24 e 48 após a cirurgia, enquanto que eletrorretinografia multifocal (mfERG) e tomografia de coerência óptica (OCT) foram realizadas antes da cirurgia e dois e doze meses após o procedimento. Os resultados da mfERG serão apresentados na forma da razão entre os valores encontrados nos dois anéis centrais, normalizados pelas médias dos três anéis periféricos (denominada razão P1), para minimizar a variabilidade interpessoal desse teste e ressaltar as alterações encontradas nos anéis centrais. A OCT foi usada para calcular o quociente entre medidas da altura e base do BM (IBM). Resultados: Quarenta e cinco pacientes (46 olhos; n = 30 BM e 16 MER) completaram as 48 semanas de seguimento. No pré-operatório, a média ± SE da MAVC (logMAR) para os grupos BM e MER, respectivamente, foi: 0,93 ± 0,22 (20/170; ou 0,12 decimal) e 0,58 ± 0,11 (20/76; ou 0,26 decimal), com melhora significativa após 48 semanas de seguimento (média ± EP da diferença entre as acuidades visuais medidas em logMAR em 48 semanas e a basal) -0,25 ± 0,07 para o grupo BM e -0,29 ± 0,06 para o grupo MER. O mfERG mostrou-se alterado antes da cirurgia para BM, com melhora da razão P1 após a cirurgia. Para o BM, houve correlação entre a razão P1 no pré-operatório e o ganho da MAVC na semana 8 após a cirurgia (r = -0,42; p = 0,033), mas essa correlação não foi observada para o grupo MER. Também não houve correlação entre o IBM e a acuidade visual após a cirurgia. Conclusões: Os resultados indicam que pacientes com BM apresentando mfERG com baixa razão P1 têm menor probabilidade de ganho de visão após a cirurgia, mas essa afirmativa não é válida para a MER. / Purpose: To evaluate retinal structure and function in eyes with macular hole (MH) or epiretinal membrane (ERM) before and after pars-plana vitrectomy with internal limitant membrane (ILM) peeling, to determine function/structural interrelations and predictive values of postoperative visual acuity. Casuistic and Methods: Fifty-one eyes of 50 patients with idiopathic MH or ERM were included. Comprehensive ophthalmologic evaluation including best-corrected visual acuity (BCVA) was performe date baseline, 1, 3, 8, 24 e 48 weeks after surgery, while optical coherence tomography (OCT) and multifocal ERG was performed before and at 2 and 12 months after surgery. mfERG results are show using the ratio between the amplitude averages of the 2 central rings and the 3 peripheral rings (P1 ratio) and OCT was used to calculate the macular hole index (MHI) defined by the quotient between hole height/base. Results: Forty-five patients (46 eyes; n = 30 MH and 16 ERM) finished follow-up. Mean ± SE (logMAR) preoperative BCVA was 0.93 ± 0.22 and 0.58 ± 0.11 for MH and ERM respectively, and improved in -0.25 ± 0.07 logMAR for MH and -0.29 ± 0.06 logMAR for ERM. mfERG P1 ratio was reduced in BM, and increased significantly after surgery. There was significant correlation between preoperative P1 ratio and BCVA gainat week 8 for MH group (r = -0,42; p = 0,033), but not for ERM group. There was no correlation between preoperative MHI and postoperative BCVA. Conclusion: This data indicates that patients with MH and poor mfERG amplitudes have worse prognoses for BCVA improvement, but does not apply for ERM.

No description available.

Lietuvoje pirmą kartą nagrinėjama daugiažidinių intraokulinių lęšių (DIOL) implantacija. Atliktas tyrimas leidžia detaliau vertinti regėjimo funkcijas po DIOL implantacijos. Keturi skirtingi DIOL lyginami pagal tą pačią meto¬diką ir pateikiami ilgos pooperacinės stebėsenos duomenys. Pirmą kartą aprašomos paciento pasitenkinimo po DIOL implantacijos ir Didžiojo penketo asmenybės dimensijų sąsajos. Darbo tikslas - įvertinti regėjimo kokybę ir pacientų pasitenkinimo rezultatais sąsajas su asmenybės bruožais po skirtingų modelių daugiažidinių intraokulinių lęšių implantacijos. Uždaviniai: 1) įvertinti regėjimo aštrumą implantavus skirtingus DIOL modelius; 2) įvertinti kontrastinį jautrumą implantavus skirtingus DIOL mo¬de¬lius; 3) įvertinti paciento poreikį papildomai korekcijai akiniais po DIOL implantacijos; 4) įvertinti pašalinių optinių fenomenų pasireiškimą su DIOL; 5) įvertinti pacientų pasitenkinimo regėjimo rezultatais dažnumą ir sąsajas su asmenybės bruožais po DIOL implantacijos. / In this study, postoperative follow-up data that cover a rather long period after the multifocal intraocular lens (MIOL) implantation are presented. It is the first time that the same methodology was used to compare four different types of MIOL. The influence of personality traits on the visual function has been defined. The aim of the study - to assess the influence of different MIOL on the quality of vision and the links between the satisfaction of patients with the results and their personality traits after the implanting of different MIOL models. The objectives of the study: 1) to compare the visual acuity between different MIOLs models; 2) to compare the contrast sensitivity between different MIOLs models; 3) to establish the need of patients for additional correction with glasses after the implanting of MIOLs; 4) to assess the occurrence of photic phenomena after the implanting of MIOLs; 5) to assess the level of visual function and the influence of personality traits on patients’ satisfaction with the visual function following the MIOL implantation.

Fluorescence lifetime imaging microscopy (FLIM) is an imaging modality that is able to provide key insights into subcellular processes. When used to measure Förster resonance energy transfer (FRET), for instance, it can discern protein-protein interactions and conformational changes. This kind of information is highly useful in the drug screening process in order to determine the effectiveness of drug leads and their mechanisms of action. FLIM has yet to be successfully translated to high-content screening (HCS) platforms due to the high throughput and fine temporal and spatial resolution requirements of HCS. Our prototype HCS FLIM system uses a time-resolving instrument called a streak camera to multiplex the FLIM scanning process, allowing for 100 confocal spots to be simultaneously scanned across a sample. There have been a few major advancements to the prototype. First the fiber array used to connect the fluorescence channels to the streak camera was characterized. Its alternating fiber delay scheme was successful in greatly reducing optical crosstalk between adjacent channels. Next, an optical beam scanner for parallel excitation beams was designed and implemented, greatly improving the possible scan speeds of the system. The streak camera was upgraded to a higher repetition rate sweep, and modifications to system components and reconstruction procedures were made to accommodate the new sweep unit. A single-photon avalanche diode array was also tested as a possible replacement for the streak camera, and was found to offer photon detection efficiency advantages. Finally, improvements were made to the excitation power and optical throughput of the system in order to reduce the required exposure time. These advances to the prototype system bring it closer to realizing the requirements of HCS FLIM, and provide a clear picture for future improvements and research directions. / Thesis / Doctor of Philosophy (PhD) / Fluorescent proteins are commonly used to tag subcellular targets so that they can easily be distinguished with a fluorescence microscope. While this can help visualize where different organelles and proteins are located in the cell, a great deal more information can be gained by measuring the fluorescence lifetime at each point in the sample, which is highly sensitive to the microenvironment. Fluorescence lifetime imaging microscopy (FLIM) has the potential to be a powerful technique for testing drug leads in the drug discovery process, although current FLIM systems are not able to provide the high throughput speeds and high temporal resolution required for drug screening. This thesis project has succeeded in improving a highly parallel FLIM microscope by reducing inter-channel crosstalk, implementing an optical scanner, improving power and optical throughput, and investigating future time-resolving instruments. This progress has brought the prototype setup closer to being used in a drug screening environment.

We report on a stem cell-transplanted patient with B cell chronic lymphatic leukemia who presented with a subacute onset of focal neurological deficits, gait abnormalities, emotional lability and dementia. Progressive multifocal leukoencephalopathy was diagnosed by magnetic resonance imaging (MRI) of the brain and detection of JC virus genome in the cerebrospinal fluid. Cidofovir and the 5HT2A receptor antagonist chlorpromazine were subsequently administered. A follow-up MRI of the brain 2 weeks after initiation of the antiviral therapy displayed progress of the demyelination, and the patient died 3 months after onset of the neurological symptoms. This report highlights the need for the development of novel and potent strategies for treatment of progressive multifocal leukoencephalopathy. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Intraocular lenses (IOLs) provide distance and near refraction and are becoming the standard for cataract surgery. Multifocal glasses increase the variability of toe clearance in older adults navigating stairs and increase fall risk; however, little is known about the biomechanics of stair navigation in individuals with multifocal IOLs. This study compared clearance while ascending and descending stairs in individuals with monofocal versus multifocal IOLs. Eight participants with multifocal IOLs (4 men, 4 women; mean age = 66.5 yr, standard deviation [SD] = 6.26) and fifteen male participants with monofocal IOLs (mean age = 69.9 yr, SD = 6.9) underwent vision and mobility testing. Motion analysis recorded kinematic and custom software-calculated clearances in three-dimensional space. No significant differences were found between groups on minimum clearance or variability. Clearance differed for ascending versus descending stairs: the first step onto the stair had the greatest toe clearance during ascent, whereas the final step to the floor had the greatest heel clearance during descent. This preliminary study indicates that multifocal IOLs have similar biomechanic characteristics to monofocal IOLs. Given that step characteristics are related to fall risk, we can speculate that multifocal IOLs carry no additional fall risk.