Search

Contains fulltext : 307329.pdf (Publisher’s version ) (Open Access)

Radboud University, 22 februari 2023, Promotores : Bloem, B.R., Hoyng, C.B. Co-promotores : Vries, N.M. de, Theelen, T., Contains fulltext : 288679.pdf (Publisher’s version ) (Closed access)

Item does not contain fulltext

Radboud University, 21 september 2022, Promotores : Ginneken, B. van, Hoyng, C.B. Co-promotores : Sanchez Gutierrez, C.I., Theelen, T., Contains fulltext : 252875.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 251558.pdf (Publisher’s version ) (Open Access), Sjögren-Larsson syndrome (SLS) is a neurometabolic disease with a peculiar crystalline maculopathy. It is yet unclear if vascular abnormalities play a role in SLS maculopathy pathogenesis. We used optical coherence tomography angiography (OCT-A) to search for vessel abnormalities in SLS maculopathy. We performed a cross-sectional study in 4 patients (2 males, 2 females, aged 12-36 years) with various stages of SLS maculopathy. Besides OCT-A imaging, a complete ophthalmological examination and additional retinal imaging by transversal and en face spectral domain (SD) OCT were performed. OCT-A images were qualitatively assessed for vascular abnormalities, and imaging was compared to eight eyes of four healthy controls. On OCT-A, all eyes of patients with SLS showed a reduced capillary density around the fovea, and an enlarged foveal avascular zone (FAZ; SLS patients [n = 6 eyes] mean 0.70 mm(2) [SD 0.18]; healthy controls [n = 8 eyes] mean 0.34 mm(2) [SD 0.07], p = 0.004). In 2 patients, telangiectatic vessels were seen in the deep capillary layer. In conclusion, OCT angiography showed capillary paucity and morphological vessel abnormalities in these 4 patients with SLS.

Contains fulltext : 251576.pdf (Publisher’s version ) (Open Access), BACKGROUND: Ophthalmological disorders are common and frequently disabling for people with Parkinson's disease (PD). However, details on the prevalence, severity and impact of ophthalmological disorders thus far lacking. We aimed to identify PD patients with undetected ophthalmological disorders in a large cross-sectional, observational study. METHODS: We previously delivered a screening questionnaire to detect ophthalmological symptoms (Visual impairment in PD questionnaire; VIPD-Q) to 848 patients. Here, we report on a subgroup of 102 patients who received complete ophthalmological assessment aimed at identifying clinically relevant ophthalmological diseases, which were classified as either vison-threatening or not. Impact on daily life functioning was measured using the visual functioning-25 questionnaire (VFQ-25) and fall frequency. RESULTS: Almost all patients (92%) had one or more clinically relevant ophthalmological disorders. Of those, 77% had a potentially vision-threatening disease, while 34% had a potentially treatable ophthalmological disease which impacted on quality of life. The most prevalent ophthalmological disorders were dry eyes (86%), ocular misalignment (50%) and convergence insufficiency (41%). We found a weak but significant association between clinically relevant ophthalmological diseases and both fall frequency (R(2) = 0.15, p = 0.037) and VFQ-25 score (R(2) = 0.15, p = 0.02). The VIPD-Q could not correctly identify patients with relevant ophthalmological disorders. CONCLUSIONS: Surprisingly, in our study sample, many participants manifested previously undetected ophthalmological diseases, most of which threatened vision, impacted on daily life functioning and were amenable to treatment. Screening for these ophthalmological disorders using a questionnaire asking about symptoms seems insufficient. Instead, episodic ophthalmological assessments should be considered for PD patients, aiming to identify vision-threatening yet treatable diseases.

Item does not contain fulltext, BACKGROUND AND OBJECTIVES: Data on the natural history of facioscapulohumeral dystrophy (FSHD) in childhood are limited and critical for improved patient care and clinical trial readiness. Our objective was to describe the disease course of FSHD in children. METHODS: We performed a nationwide, single-center, prospective cohort study of FSHD in childhood assessing muscle functioning, imaging, and quality of life over 2 years of follow-up. RESULTS: We included 20 children with genetically confirmed FSHD who were 2 to 17 years of age. Overall, symptoms were slowly progressive, and the mean FSHD clinical score increased from 2.1 to 2.8 (p = 0.003). The rate of progression was highly variable. At baseline, 16 of 20 symptomatic children had facial weakness; after 2 years, facial weakness was observed in 19 of 20 children. Muscle strength did not change between baseline and follow-up. The most frequently and most severely affected muscles were the trapezius and deltoid. The functional exercise capacity, measured with the 6-minute walk test, improved. Systemic features were infrequent and nonprogressive. Weakness-associated complications such as lumbar hyperlordosis and dysarthria were common, and their prevalence increased during follow-up. Pain and fatigue were frequent complaints in children, and their prevalence also increased during follow-up. Muscle ultrasonography revealed a progressive increase in echogenicity. DISCUSSION: FSHD in childhood has a slowly progressive but variable course over 2 years of follow-up. The most promising outcome measures to detect progression were the FSHD clinical score and muscle ultrasonography. Despite this disease progression, an improvement on functional capacity may still occur as the child grows up. Pain, fatigue, and a decreased quality of life were common symptoms and need to be addressed in the management of childhood FSHD. Our data can be used to counsel patients and as baseline measures for treatment trials in childhood FSHD.

Contains fulltext : 235080.pdf (Publisher’s version ) (Open Access)

Radboud University, 20 mei 2021, Promotor : Willemsen, M.A.A.P. Co-promotor : Theelen, T., Contains fulltext : 232643.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 243941.pdf (Publisher’s version ) (Open Access), PURPOSE: To evaluate reliability and repeatability of computer-assisted measurements of cone photoreceptor metrics on Heidelberg Engineering Spectralis™ High Magnification Module (HMM™) Automatic Real-time Tracking (ART™) images. METHODS: We analyzed HMM™ images in three separate study arms. Computer-assisted cone identification software was validated using an open-access adaptive optics (AO) dataset. We compared results of the first arm to data from AO and histology. We evaluated intersession repeatability of our computer-assisted cone analysis in the second arm. We assessed the capability of HMM™ to visualize cones in the presence of pathology in the third arm. RESULTS: We included 10 healthy subjects in the first arm of our study, 5 additional healthy participants in the second arm and 5 patients in the third arm. In total, we analyzed 225 regions of interest on HMM™ images. We were able to automatically identify cone photoreceptors and assess corresponding metrics at all eccentricities between 2 and 9° from the fovea. Cone density significantly declined with increasing eccentricity (p = 4.890E-26, Friedman test). With increasing eccentricity, we found a significant increase in intercell distance (p = 2.196E-25, Friedman test) and nearest neighbor distance (p = 1.997E-25, Friedman test). Cone hexagonality ranged between 71 and 85%. We found excellent automated intersession repeatability of cone density counts and spacing measurements. In pathology, we were also able to repeatedly visualize photoreceptors. CONCLUSION: Computer-assisted cone photoreceptor analysis on Spectralis™ HMM™ images is feasible, and most cone metrics show excellent repeatability. HMM™ imaging may be useful for photoreceptor analysis as progression marker in outer retinal disease.

Contains fulltext : 219266.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 220549.pdf (publisher's version ) (Open Access), Sjögren-Larsson syndrome (SLS) is a rare inborn error of lipid metabolism. The syndrome is caused by mutations in the ALDH3A2 gene, resulting in a deficiency of fatty aldehyde dehydrogenase. Most patients have a clearly recognizable severe phenotype, with congenital ichthyosis, intellectual disability, and spastic diplegia. In this study, we describe two patients with a remarkably mild phenotype. In both patients, males with actual ages of 45 and 61 years, the diagnosis was only established at an adult age. Their skin had been moderately affected from childhood onward, and both men remained ambulant with mild spasticity of their legs. Cognitive development, as reflected by school performance and professional career, had been unremarkable. Magnetic resonance spectroscopy of the first patient was lacking the characteristic lipid peak. We performed a literature search to identify additional SLS patients with a mild phenotype. We compared the clinical, radiologic, and molecular features of the mildly affected patients with the classical phenotype. We found 10 cases in the literature with a molecular proven diagnosis and a mild phenotype. Neither a genotype-phenotype correlation nor an alternative explanation for the strikingly mild phenotypes was found. New biochemical techniques to study the underlying metabolic defect in SLS, like lipidomics, may in the future help to unravel the reasons for the exceptionally mild phenotypes. In the meantime, it is important to recognize these mildly affected patients to provide them with appropriate care and genetic counseling, and to increase our insights in the true disease spectrum of SLS.

Radboud University, 15 januari 2020, Promotores : Opstal, A.J. van, Berg, A.V. van den Co-promotores : Goossens, H.H.L.M., Theelen, T., Contains fulltext : 214169.pdf (publisher's version ) (Open Access)

Item does not contain fulltext

Contains fulltext : 226267.pdf (publisher's version ) (Open Access)

Contains fulltext : 205535.pdf (publisher's version ) (Open Access), BACKGROUND: Visual disorders are common in Parkinson's disease (PD) but their exact frequency and severity are unknown. Good visual functioning is crucial for patients with PD, because of their need to compensate for loss of automated motor control and their postural instability, forcing patients to guide their movements visually. Here, we describe the study design of a cross-sectional, multi-centre study aiming to: (1) validate the Visual Impairment screening questionnaire (VIPD-Q, which aims to identify PD patients who should be referred to an ophthalmologist for further assessment); (2) study the prevalence of visual disorders in PD; (3) study the severity and clinical impact of different types of visual disorders in PD; and (4) explore treatment options for ophthalmologic disorders in PD, as a basis for future guideline development. METHODS: This study consists of two phases. In phase one, 750 PD patients and 250 healthy controls will be recruited to complete the VIPD-Q. In phase two, a subgroup of responders (n = 100) (with the highest and lowest scores on the VIPD-Q) will be invited for an extensive neurological and ophthalmological assessment. The in-depth ophthalmologic examination will serve as the "gold standard" for validating the VIPD-Q. Moreover, these assessments will be used to study associations between visual disorders and clinical presentation, in order to gain more insight in their clinical impact. DISCUSSION: Our study will heighten the awareness of visual problems in PD and offers a robust starting point to systematically approach this subject. In current daily practice, the association between visual problems and PD is far from obvious to both patients and clinicians. Consequently, patients may not adequately report visual problems themselves, while clinicians miss potentially treatable visual disorders. Routinely asking patients to complete a simple screening questionnaire could be an easy solution leading to timely identification of visual pr

Item does not contain fulltext

Contains fulltext : 204162.pdf (publisher's version ) (Closed access), PURPOSE: To study long-term macular changes by spectral-domain (SD) OCT in patients with Sjogren-Larsson syndrome (SLS). DESIGN: Retrospective cohort study. PARTICIPANTS: Twenty-two patients with genetically proven SLS (12 female, 10 male; median age, 21 years; range, 3-47 years) were included in the study. One or more SD-OCT scans were available from the period 2008 to 2017. METHODS: Seventeen patients underwent SD-OCT imaging of the macula in 2017. Earlier scans were available of the other 5 patients. The latest available SD-OCT scans were qualitatively assessed for morphologic changes in 19 patients. In addition, retinal layer thickness could be measured in 15 patients. The latest scans were compared with previous scans to assess the course of the disease qualitatively (n = 15 patients) and quantitatively (n = 10 patients). MAIN OUTCOME MEASURES: Macular morphology and retinal layer thickness on SD-OCT scans during the study period. RESULTS: In all patients, abnormal macular morphology was observed in both eyes, already from the youngest age. Intraretinal crystals, visible as hyperreflective dots, were visible in all eyes and located in the retinal nerve fiber layer, inner plexiform layer, and outer plexiform layer. Furthermore, the photoreceptor (PR) layer lacked the physiologic thickness amplification beneath the fovea. Pseudocysts with limited interruption of the underlying PR layer were observed in half of the patients, all younger than 30 years of age. Frank atrophy of the retinal pigment epithelium (RPE) and a neovascular complex were seen in 3 older patients and 1 older patient, respectively. The fovea was significantly thinner compared with healthy controls and decreased even further during the study period. CONCLUSIONS: Macular dystrophy in SLS may initially comprise an arrest in foveal development. Because of the absence of macular pigment, phototoxic damage may then cause central retinal degeneration of the vulnerable macula, marked by the development

Radboud University, 10 december 2019, Promotores : Ginneken, B. van, Hoyng, C.B. Co-promotores : Sanchez Gutierrez, C.I., Theelen, T., Contains fulltext : 212465.pdf (publisher's version ) (Open Access)

Item does not contain fulltext, PURPOSE: To assess the short-term outcome of and possible temporary vision loss after half-dose verteporfin photodynamic therapy (PDT) in patients with chronic central serous chorioretinopathy (cCSC). METHODS: In this prospective study, 14 eyes of 13 cCSC patients who underwent half-dose PDT were included. Patients received spectral-domain optical coherence tomography (OCT) imaging and microperimetry before PDT on the day of treatment and 1 week after treatment. RESULTS: Five patients (38%) reported worsening of visual complaints in the week after half-dose PDT. No significant changes in both central foveal thickness, height of subretinal fluid, and choroidal thickness on optical coherence tomography imaging and retinal sensitivity on microperimetry were observed, neither in the patients who did not experience worsening of visual symptoms, nor in those who did. CONCLUSION: Worsening of visual complaints can occur in a noteworthy number of cCSC patients in the first week after half-dose verteporfin PDT. Despite the fact that no significant short-term changes on both optical coherence tomography and microperimetry have been detected in this study, the assessment could be of importance for the long-term outcome of treatment and needs further investigation.

Contains fulltext : 195437.pdf (publisher's version ) (Open Access)

Item does not contain fulltext, Optical coherence tomography (OCT) is a high-resolution, three-dimensional, noninvasive imaging modality to examine the human retina. Since the introduction of spectral domain (SD-) OCT-the currently most used variant of OCT-previously unknown details of in vivo retinal morphology of a broad variety of pathologies have become visible. This chapter explains the basic principles of the OCT technology, deals with possible pitfalls in OCT examination or analysis, and hints at the use of OCT technology in functional imaging.

Contains fulltext : 198456.pdf (publisher's version ) (Open Access)

Contains fulltext : 191434.pdf (publisher's version ) (Open Access)

Item does not contain fulltext

Contains fulltext : 191291.pdf (publisher's version ) (Open Access), We developed a deep learning algorithm for the automatic segmentation and quantification of intraretinal cystoid fluid (IRC) in spectral domain optical coherence tomography (SD-OCT) volumes independent of the device used for acquisition. A cascade of neural networks was introduced to include prior information on the retinal anatomy, boosting performance significantly. The proposed algorithm approached human performance reaching an overall Dice coefficient of 0.754 ± 0.136 and an intraclass correlation coefficient of 0.936, for the task of IRC segmentation and quantification, respectively. The proposed method allows for fast quantitative IRC volume measurements that can be used to improve patient care, reduce costs, and allow fast and reliable analysis in large population studies.

Contains fulltext : 170506.pdf (publisher's version ) (Open Access), PURPOSE: Current standards and guidelines aimed at preventing retinal phototoxicity during intentional exposures do not specifically evaluate the contribution of endogenous photosensitizers. However, certain retinal diseases are characterized by abnormal accumulations of potential photosensitizers such as lipofuscin bisretinoids in the retinal pigment epithelium (RPE). We sought to determine these contributions by a numerical assessment of in-vivo photo-oxidative stress during irradiation of RPE lipofuscin. METHODS: Based on the literature, we calculated the retinal exposure levels, optical filtering of incident radiation by the ocular lens, media, photoreceptors, and RPE melanin, light absorption by lipofuscin, and photochemical effects in the RPE in two situations: exposure to short-wavelength (lambda = 488 nm) fundus autofluorescence (SW-AF) excitation light and exposure to indirect (diffuse) sunlight. RESULTS: In healthy persons at age 20, 40, and 60, respectively, the rate of oxygen photoconsumption by lipofuscin increases by 1.3, 1.7, and 2.4 fold during SW-AF-imaging as compared to diffuse sunlight. In patients with STGD1 below the age of 30, this rate was 3.3-fold higher compared to age-matched controls during either sunlight or SW-AF imaging. CONCLUSIONS: Our results suggest that the RPE of patients with STGD1 is generally at increased risk of photo-oxidative stress, while exposure during SW-AF-imaging amplifies this risk. These theoretical results have not yet been verified with in-vivo data due to a lack of sufficiently sensitive in-vivo measurement techniques.

Contains fulltext : 174703.pdf (Publisher’s version ) (Open Access), Purpose: To evaluate a machine learning algorithm that automatically grades age-related macular degeneration (AMD) severity stages from optical coherence tomography (OCT) scans. Methods: A total of 3265 OCT scans from 1016 patients with either no signs of AMD or with signs of early, intermediate, or advanced AMD were randomly selected from a large European multicenter database. A machine learning system was developed to automatically grade unseen OCT scans into different AMD severity stages without requiring retinal layer segmentation. The ability of the system to identify high-risk AMD stages and to assign the correct severity stage was determined by using receiver operator characteristic (ROC) analysis and Cohen's kappa statistics (kappa), respectively. The results were compared to those of two human observers. Reproducibility was assessed in an independent, publicly available data set of 384 OCT scans. Results: The system achieved an area under the ROC curve of 0.980 with a sensitivity of 98.2% at a specificity of 91.2%. This compares favorably with the performance of human observers who achieved sensitivities of 97.0% and 99.4% at specificities of 89.7% and 87.2%, respectively. A good level of agreement with the reference was obtained (kappa = 0.713) and was in concordance with the human observers (kappa = 0.775 and kappa = 0.755, respectively). Conclusions: A machine learning system capable of automatically grading OCT scans into AMD severity stages was developed and showed similar performance as human observers. The proposed automatic system allows for a quick and reliable grading of large quantities of OCT scans, which could increase the efficiency of large-scale AMD studies and pave the way for AMD screening using OCT.

Contains fulltext : 177930.pdf (publisher's version ) (Open Access), We developed a fully automated system using a convolutional neural network (CNN) for total retina segmentation in optical coherence tomography (OCT) that is robust to the presence of severe retinal pathology. A generalized U-net network architecture was introduced to include the large context needed to account for large retinal changes. The proposed algorithm outperformed qualitative and quantitatively two available algorithms. The algorithm accurately estimated macular thickness with an error of 14.0 +/- 22.1 microm, substantially lower than the error obtained using the other algorithms (42.9 +/- 116.0 microm and 27.1 +/- 69.3 microm, respectively). These results highlighted the proposed algorithm's capability of modeling the wide variability in retinal appearance and obtained a robust and reliable retina segmentation even in severe pathological cases.

Item does not contain fulltext, Patients with Parkinson's disease (PD) often compensate for their motor deficits by guiding their movements visually. A wide range of ocular and visual disorders threatens the patients' ability to benefit optimally from visual feedback. These disorders are common in patients with PD, yet they have received little attention in both research and clinical practice, leading to unnecessary - but possibly treatable - disability. Based on a literature search covering 50 years, we review the range of ocular and visual disorders in patients with PD, and classify these according to anatomical structures of the visual pathway. We discuss six common disorders in more detail: dry eyes; diplopia; glaucoma and glaucoma-like visual problems; impaired contrast and colour vision; visuospatial and visuoperceptual impairments; and visual hallucinations. In addition, we review the effects of PD-related pharmacological and surgical treatments on visual function, and we offer practical recommendations for clinical management. Greater awareness and early recognition of ocular and visual problems in PD might enable timely instalment of tailored treatments, leading to improved patient safety, greater independence, and better quality of life.

Contains fulltext : 181865.pdf (publisher's version ) (Open Access), We propose a method for automatic detection of the foveal center in optical coherence tomography (OCT). The method is based on a pixel-wise classification of all pixels in an OCT volume using a fully convolutional neural network (CNN) with dilated convolution filters. The CNN-architecture contains anisotropic dilated filters and a shortcut connection and has been trained using a dynamic training procedure where the network identifies its own relevant training samples. The performance of the proposed method is evaluated on a data set of 400 OCT scans of patients affected by age-related macular degeneration (AMD) at different severity levels. For 391 scans (97.75%) the method identified the foveal center with a distance to a human reference less than 750 mum, with a mean (+/- SD) distance of 71 mum +/- 107 mum. Two independent observers also annotated the foveal center, with a mean distance to the reference of 57 mum +/- 84 mum and 56 mum +/- 80 mum, respectively. Furthermore, we evaluate variations to the proposed network architecture and training procedure, providing insight in the characteristics that led to the demonstrated performance of the proposed method.

Contains fulltext : 181708.pdf (publisher's version ) (Open Access), The useful-field-of-view (UFOV) test measures the amount of information someone can extract from a visual scene in one glance. Its scores show relatively strong relationships with everyday activities. The UFOV test consists of three computer tests, suggested to measure processing speed and central vision, divided attention, and selective attention. However, other functions seem to be involved as well. In order to investigate the contribution of these suggested and other perceptual and cognitive functions, we performed a meta-analysis of 116 Pearson's correlation coefficients between UFOV scores and other test scores reported in 18 peer-reviewed articles. We divided these correlations into nine domains: attention, executive functioning, general cognition, memory, spatial ability, visual closure, contrast sensitivity, visual processing speed, and visual acuity. A multivariate mixed-effects model analysis revealed that each domain correlated significantly with each of the UFOV subtest scores. These correlations were stronger for Subtests 2 and 3 than for Subtest 1. Furthermore, some domains were more strongly correlated to the UFOV than others across subtests. We did not find interaction effects between subtest and domain, indicating that none of the UFOV subtests is more selectively sensitive to a particular domain than the others. Thus, none of the three UFOV subtests seem to measure one clear construct. Instead, a range of visual and cognitive functions is involved. Perhaps this is the reason for the UFOV's high ecological validity, as it involves many functions at once, making it harder to compensate if one of them fails.