| 1. |
- Björkman, Kristoffer, et al.
(författare)
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Clinical course of patients with single large-scale mtDNA deletions and childhood onset anemia
- 2022
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Ingår i: 14th European Paediatric Neurology Society Congress, Glasgow, UK (ISBN 978-3-00-072065-9).
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Objective: To add to our knowledge of the clinical spectrum of patients with single large-scale mitochondrial DNA (mtDNA) deletion and childhood onset anemia. Methods: Retrospective collection of clinical data from medical records for patients, both living and deceased, with a single large-scale mtDNA deletion from seven mitochondrial disease centers in five countries. Statistical analysis with descriptive methods and Kaplan-Meier survival analysis. Results: Seventeen patients matching the genetic criterium and with anemia onset before six years of age. Exocrine pancreatic insufficiency was only seen in five patients in this group. Multiple organs were involved in all patients, with the most common non-hematologic ones being skeletal muscle, central nervous system, endocrine, eyes, gastrointestinal system, kidneys, hearing, liver and heart. Psychomotor retardation was seen in ten patients, hearing impairment in nine patients, failure to thrive in eight patients. Eight later developed Kearns-Sayre syndrome. Eleven patients were deceased, with a median age at death of 7.5 years. Conclusions: The classically described phenotype of patients with large-scale mtDNA deletions and early onset anemia is Pearson marrow-pancreas syndrome, characterized by sideroblastic anemia and exocrine pancreas dysfunction. Only a minority of our patients fulfill the original criteria of Pearson syndrome though. Involvement of other organs than the pancreas is more common. The clinical course vary, but multi-system impact is the rule and life-expectancy is low. Early onset anemia in patients with large-scale mtDNA deletions is most frequently not associated with exocrine pancreas dysfunction. Better knowledge of the phenotype is helpful for diagnosis and more accurate prognosis.
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| 2. |
- Pivodic, Aldina, 1978, et al.
(författare)
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Individual Risk Prediction for Sight-Threatening Retinopathy of Prematurity Using Birth Characteristics
- 2020
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Ingår i: JAMA Ophthalmology. - : American Medical Association (AMA). - 2168-6165 .- 2168-6173. ; 138:1, s. 21-29
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Tidskriftsartikel (refereegranskat)abstract
- Importance: To prevent blindness, repeated infant eye examinations are performed to detect severe retinopathy of prematurity (ROP), yet only a small fraction of those screened need treatment. Early individual risk stratification would improve screening timing and efficiency and potentially reduce the risk of blindness. Objectives: To create and validate an easy-to-use prediction model using only birth characteristics and to describe a continuous hazard function for ROP treatment. Design, Setting, and Participants: In this retrospective cohort study, Swedish National Patient Registry data from infants screened for ROP (born between January 1, 2007, and August 7, 2018) were analyzed with Poisson regression for time-varying data (postnatal age, gestational age [GA], sex, birth weight, and important interactions) to develop an individualized predictive model for ROP treatment (called DIGIROP-Birth [Digital ROP]). The model was validated internally and externally (in US and European cohorts) and compared with 4 published prediction models. Main Outcomes and Measures: The study outcome was ROP treatment. The measures were estimated momentary and cumulative risks, hazard ratios with 95% CIs, area under the receiver operating characteristic curve (hereinafter referred to as AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results: Among 7609 infants (54.6% boys; mean [SD] GA, 28.1 [2.1] weeks; mean [SD] birth weight, 1119 [353] g), 442 (5.8%) were treated for ROP, including 142 (40.1%) treated of 354 born at less than 24 gestational weeks. Irrespective of GA, the risk for receiving ROP treatment increased during postnatal weeks 8 through 12 and decreased thereafter. Validations of DIGIROP-Birth for 24 to 30 weeks' GA showed high predictive ability for the model overall (AUC, 0.90 [95% CI, 0.89-0.92] for internal validation, 0.94 [95% CI, 0.90-0.98] for temporal validation, 0.87 [95% CI, 0.84-0.89] for US external validation, and 0.90 [95% CI, 0.85-0.95] for European external validation) by calendar periods and by race/ethnicity. The sensitivity, specificity, PPV, and NPV were numerically at least as high as those obtained from CHOP-ROP (Children's Hospital of Philadelphia-ROP), OMA-ROP (Omaha-ROP), WINROP (weight, insulinlike growth factor 1, neonatal, ROP), and CO-ROP (Colorado-ROP), models requiring more complex postnatal data. Conclusions and Relevance: This study validated an individualized prediction model for infants born at 24 to 30 weeks' GA, enabling early risk prediction of ROP treatment based on birth characteristics data. Postnatal age rather than postmenstrual age was a better predictive variable for the temporal risk of ROP treatment. The model is an accessible online application that appears to be generalizable and to have at least as good test statistics as other models requiring longitudinal neonatal data not always readily available to ophthalmologists.
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| 3. |
- Rocha, João Victor, et al.
(författare)
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Trends, geographical variation and factors associated with the use of anti-VEGF intravitreal injections in Portugal (2013–2018): a retrospective analysis of administrative data
- 2022
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 12:4
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Tidskriftsartikel (refereegranskat)abstract
- Aims The arrival of anti-vascular endothelial growth factor (anti-VEGF) therapies represented a treatment shift for several ophthalmological disorders and led to an increasing number of patients undergoing intravitreal injections. The aims of this observational study were to assess the expansion of anti-VEGF intravitreal injections in the Portuguese National Health System (NHS) and to identify factors correlated with geographical variations in episode rates.Methods Administrative database on discharge from Portuguese NHS hospitals was analysed for annual values and rates of intravitreal anti-VEGF injections at a national and regional level, between 2013 and 2018.Results The number of episodes of anti-VEGF treatment and patients treated increased 16% and 9% per year, respectively, between 2013 and 2018. During the study period around 72% of patients were treated in the Metropolitan areas of Lisbon and Porto and in the Central region. Intravitreal anti-VEGF treatment rates in 2018 were 560 per 100 000 population and presented high variability between municipalities. Higher anti-VEGF treatment rates at the municipality level were associated with shorter distances between their residence and the hospital. At the hospital level, higher ratio of ophthalmologists and higher organisational level were associated with higher anti-VEGF treatment rates.Conclusion The number of episodes and patients treated with anti-VEGF injections has been growing in recent years. Proximity to healthcare, more access to ophthalmologists and hospitals with higher organisational levels are associated with higher anti-VEGF treatment rates. Improving access is crucial to reduce regional discrepancies and ensure optimal treatment frequency, which may improve health outcomes.
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| 4. |
- Jacobson, Lena, et al.
(författare)
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Retinal ganglion cell topography predicts visual field function in spastic cerebral palsy
- 2020
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Ingår i: Developmental Medicine and Child Neurology. - : Wiley. - 0012-1622 .- 1469-8749. ; 62:9, s. 1100-1106
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate the use of optical coherence tomography (OCT) to identify and assess visual field defects caused by primary damage to the optic radiation in individuals with spastic cerebral palsy (CP). Ten individuals with spastic CP (six females, four males, with a median age of 21 years [range 17–38y]) had their brain lesions documented with conventional magnetic resonance imaging (MRI) and diffusion-weighted MRI fibre tractography. Their macular ganglion cell layer (GCL) and inner plexiform layer (IPL) were examined with OCT and their visual fields were plotted. All participants had good visual acuity and were able to cooperate with the MRI and OCT examinations, as well as undergoing reliable perimetry. We found focal thinning of the GCL+IPL and corresponding homonymous visual field defects in individuals with brain damage affecting the optic radiation. We used GCL+IPL sector asymmetry as a sensitive OCT parameter to identify focal visual field defects. We observed no such sector asymmetry in GCL+IPL, or focal visual field defects, in individuals with normal MRI optic radiation imaging. Lesions affecting the optic radiation cause retrograde trans-synaptic degeneration of retinal ganglion cells. OCT examination of the GCL in the macula identified corresponding focal damage to the optic radiation in individuals with spastic CP and can be used to predict focal visual field defects. What this paper adds: Spastic cerebral palsy (CP) may be associated with damage to the optic radiation. Damage to the optic radiation causes retrograde trans-synaptic degeneration (RTSD). RTSD can be mapped using optical coherence tomography. Ganglion cell topography can predict visual field defects in individuals with spastic CP.
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| 5. |
- Konstantinou, Konstantinos, 1993, et al.
(författare)
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Statistical modeling of diabetic neuropathy: Exploring the dynamics of nerve mortality
- 2023
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Ingår i: Statistics in Medicine. - 0277-6715 .- 1097-0258. ; 42:23, s. 4128-4146
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Tidskriftsartikel (refereegranskat)abstract
- Diabetic neuropathy is a disorder characterized by impaired nerve function and reduction of the number of epidermal nerve fibers per epidermal surface. Additionally, as neuropathy related nerve fiber loss and regrowth progresses over time, the two-dimensional spatial arrangement of the nerves becomes more clustered. These observations suggest that with development of neuropathy, the spatial pattern of diminished skin innervation is defined by a thinning process which remains incompletely characterized. We regard samples obtained from healthy controls and subjects suffering from diabetic neuropathy as realisations of planar point processes consisting of nerve entry points and nerve endings, and propose point process models based on spatial thinning to describe the change as neuropathy advances. Initially, the hypothesis that the nerve removal occurs completely at random is tested using independent random thinning of healthy patterns. Then, a dependent parametric thinning model that favors the removal of isolated nerve trees is proposed. Approximate Bayesian computation is used to infer the distribution of the model parameters, and the goodness-of-fit of the models is evaluated using both non-spatial and spatial summary statistics. Our findings suggest that the nerve mortality process changes as neuropathy advances.
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| 6. |
- Granstam, Elisabet, 1963-, et al.
(författare)
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Long‐term follow‐up of antivascular endothelial growth factor treatment for diabetic macular oedema : a four‐year real‐world study
- 2020
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Ingår i: Acta Ophthalmologica. - : Wiley. - 1755-375X .- 1755-3768. ; 98:4, s. 360-367
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Tidskriftsartikel (refereegranskat)abstract
- PurposeTo evaluate visual acuity (VA) and central retinal thickness (CRT) on optical coherence tomography during a 4‐year period in patients treated for sight‐threatening diabetic macular oedema (DMO) at two Swedish county hospitals. Additionally, to compare health‐related quality of life and subjective visual functioning before and after 4 years of treatment.MethodsFifty‐eight patients with DMO were evaluated after 4 years of antivascular endothelial growth factor (VEGF) treatment. VA, CRT and clinical data were retrospectively reviewed. Health‐related quality of life and subjective visual functioning were evaluated with Short Form Health Survey (SF‐36) and National Eye Institute Vision Functioning Questionnaire 25 (VFQ‐25). Comparisons between independent groups were performed using Pearson's χ2 test, Fisher's exact test or Mann–Whitney U test. Spearman's ρ was used for correlation analyses. Wilcoxon signed‐rank test was used for comparison between dependent groups. Logistic regression analysis was applied for analysis of VA and CRT over 4 years.ResultsFollow‐up data were obtained from 37 of 58 (63.8%) patients. Baseline characteristics were similar, regardless of follow‐up. VA improvement at 1 year (mean + 4.4, SD 7.5; ETDRS letter score) was maintained over 3 years, then declined. CRT was reduced throughout the study. In the first treatment year, eyes received 5.1 (1.4) anti‐VEGF injections, followed by approximately two injections yearly. Additional treatment included laser and dexamethasone implants. SF‐36 showed no change at 4 years, compared with baseline. VFQ‐25 demonstrated improvement in near vision activities (p = 0.036).ConclusionSignificant long‐term improvement in visual function was present in patients with anti‐VEGF‐treated DMO.
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| 7. |
- Hector, Sven, et al.
(författare)
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Soluble CD163 and glycated haemoglobin were independently associated with the progression of diabetic retinopathy in adult patients with type 1 diabetes
- 2023
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Ingår i: BMJ Open Ophthalmology. - : BMJ Publishing Group Ltd. - 2397-3269. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveHigh vitreous levels of soluble (s)CD163 have been demonstrated in severe diabetic retinopathy (DR). The aim of this study was to explore the predictive values of plasma sCD163 and glycated haemoglobin (HbA1c) for DR progression in adults with type 1 diabetes. Methods and analysesThe study design was prospective. Fundus photography performed in 2009 and at follow-up (& LE;12 years later) were compared after being categorised according to the International Clinical Diabetic Retinopathy Disease Severity Scale. 'DR progression at least one level' was calculated. In 2009, data collection (sex, age, diabetes duration, metabolic variables, serum creatinine, macroalbuminuria and lifestyle factors) and biochemical analyses were performed. Plasma sCD163 and HbA1c were divided into quartiles. Logistic regression analyses were performed. ResultsThe prevalence of DR in 2009 versus at follow-up in 270 participants (57% male) were: no apparent 28% vs 18%; mild 20% vs 13%; moderate 24% vs 26%; severe 11% vs 13%; and proliferative DR 17% vs 30% (p<0.001). DR progression occurred in 101 (45%) patients. HbA1c & GE;54 mmol/mol (& GE;7.1%) (>1st quartile) (adjusted odds ratio (AOR) 3.8, p<0.001) and sCD163 & GE;343 ng/mL (>1st quartile) (AOR 2.6, p=0.004) were independently associated with DR progression. The associations with DR progression increased significantly from the first to the fourth quartile for HbA1c (AORs: 1; 2.5; 3.6; 7.4), but not for sCD163 (AORs: 1; 2.9; 2.4; 2.4). ConclusionPlasma sCD163 may constitute a valuable biomarker for DR progression in addition to and independent of the well-established biomarker HbA1c.
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| 8. |
- Huang, X. F., et al.
(författare)
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Genomewide Association Study of Acute Anterior Uveitis Identifies New Susceptibility Loci
- 2020
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Ingår i: Investigative Ophthalmology & Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 61:6
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. Acute anterior uveitis (AAU) is a common intraocular inflammatory disease. AAU occurs in 30% to 50% of patients with ankylosing spondylitis (AS), and both conditions are strongly associated with human leukocyte antigen (HLA)-B 27 , implying a shared etiology. This study aims to apply genomewide association study (GWAS) to characterize the genetic associations of AAU and their relationship to the genetics of AS. METHODS. We undertook the GWAS analyses in 2752 patients with AS with AAU (cases) and 3836 patients with AS without AAU (controls). There were 7,436,415 single-nucleotide polymorphisms (SNPs) available alter SNP microarray genotyping, imputation, and quality-control filtering. RESULTS. We identified one locus associated with AAU at genomewide significance: rs9378248 (P = 2.69 x 10(-8), odds ratio [OR] = 0.78), lying close to HLA-B. Suggestive association was observed at 11 additional loci, including previously reported AS loci ERAP1 (rs27529, P = 2.19 x 10(-7), OR = 1.22) and NOS2 (rs2274894, P = 8.22 x 10(-7), OR = 0.83). Multiple novel suggestive associations were also identified, including MERTK (rsl0171979, P = 2.56 x 10(-6), OR = 1.20), KIFAP3 (rs508063, P = 5.64 x 10(-7), OR = 1.20), CLCN7 (rs67412457, P = 1.33 x 10(-6), OR = 1.25), ACAA2 (rs9947182, P = 9.70 x 10(-7), OR = 1.37), and 5 intergenic loci. The SNP-based heritability is approximately 0.5 for AS alone, and is much higher (approximately 0.7) for AS with AAU. Consistent with the high heritability, a genomewide polygenic risk score shows strong power in identifying individuals at high risk of either AS with AAU or AS alone. CONCLUSIONS. We report here the first GWAS for AAU and identify new susceptibility loci. Our findings confirm the strong overlap in etiopathogenesis of AAU with AS, and also provide new insights into the genetic basis of AAU.
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| 9. |
- Holmström, Gerd, 1951-, et al.
(författare)
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New modifications of Swedish ROP guidelines based on 10-year data from the SWEDROP register
- 2020
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Ingår i: British Journal of Ophthalmology. - : BMJ. - 0007-1161 .- 1468-2079. ; 104:7, s. 943-949
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/AIMS:During the last decade, improved neonatal care has resulted in increased survival of the most immature infants and improved health of more mature infants. We hypothesise that this has affected incidence and treatment of retinopathy of prematurity (ROP), enabling guidelines for screening to be modified.METHODS: In Sweden, all infants with gestational age (GA) at birth ≤30 weeks are screened for ROP. Results are registered in a web-based register, Swedish National ROP Register, with a coverage rate of 97%. Incidence of ROP and frequency of treatment, aspects on natural course of ROP and number of examinations, are calculated in relation to GA at birth in infants born during 2008-2017.RESULTS: Of 7249 infants, 31.9% (2310) had ROP and 6.1% (440) were treated. No infant with GA 30 weeks was treated. Incidence of ROP remained similar, but frequency of treatment increased (p=0.023). Over time, GA and birth weight were reduced in infants with ROP and with treated ROP. In the most immature infants, postmenstrual age was lower and postnatal age was higher when any ROP and stage 3 ROP were first detected (p<0.001). At treatment, postmenstrual but not postnatal age of the infant was associated with GA (p<0.001). During the 10-year period, 46 038 examinations were performed.CONCLUSION: Modification of Swedish guidelines is proposed, including only infants with a GA of <30 weeks and postponing the first examination with 1 week in infants with GA 26-29 weeks. This would spare many infants from stressful examinations and reduce eye examinations with at least 20%.
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| 10. |
- Hult, Jenny, et al.
(författare)
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Comparison of photoacoustic imaging and histopathological examination in determining the dimensions of 52 human melanomas and nevi ex vivo : Biomedical Optics Express
- 2021
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Ingår i: Biomedical Optics Express. - 2156-7085. ; 12:7, s. 4097-4114
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Tidskriftsartikel (refereegranskat)abstract
- Surgical excision followed by histopathological examination is the gold standard for the diagnosis and staging of melanoma. Reoperations and unnecessary removal of healthy tissue could be reduced if non-invasive imaging techniques were available for presurgical tumor delineation. However, no technique has gained widespread clinical use to date due to shallow imaging depth or the absence of functional imaging capability. Photoacoustic (PA) imaging is a novel technology that combines the strengths of optical and ultrasound imaging to reveal the molecular composition of tissue at high resolution. Encouraging results have been obtained from previous animal and human studies on melanoma, but there is still a lack of clinical data. This is the largest study of its kind to date, including 52 melanomas and nevi. 3D multiwavelength PA scanning was performed ex vivo, using 59 excitation wavelengths from 680 nm to 970 nm. Spectral unmixing over this broad wavelength range, accounting for the absorption of several tissue chromophores, provided excellent contrast between healthy tissue and tumor. Combining the results of spectral analysis with spatially resolved information provided a map of the tumor borders in greater detail than previously reported. The tumor dimensions determined with PA imaging were strongly correlated with those determined by histopathological examination for both melanomas and nevi.
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