| 1. |
- Boulakh, Lena, et al.
(author)
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Thyroid dysfunction and exudative age-related macular degeneration - A longitudinal nationwide registry-based cohort study
- 2024
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In: ACTA OPHTHALMOLOGICA. - 1755-375X .- 1755-3768.
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Journal article (peer-reviewed)abstract
- Purpose: The association between thyroid dysfunction and exudative age-related macular degeneration (AMD) is unknown. Methods: In this Danish longitudinal nationwide registry-based cohort study we included all Danish residents aged 50-100 between 2008 and 2018. Using the Danish national registries, we studied the association between thyroid dysfunction and exudative AMD. Thyroid dysfunction was classified as two consecutive redeemed prescriptions of thyroid hormones (hypothyroidism) or anti-thyroid medication (hyperthyroidism). Exudative AMD was classified as an ICD diagnosis of AMD and a code for anti-VEGF treatment. All patients are treated for exudative AMD in a hospital in Denmark, and we therefore have complete registration of this patient group. Results: We included 2 087 305 individuals, of which 1 072 567 (51.4%) were women; 59 318 (2.8%) had hypothyroidism, and 33 922 (1.6%) had hyperthyroidism. During a median follow-up of 11 years, 26 998 (1.3%) people developed exudative AMD. Hypothyroidism (adjusted hazard ratio [HR]: 1.17; 95% confidence interval [CI] 1.10-1.25; p < 0.001) and hyperthyroidism (HR: 1.23; 95% CI:1.13-1.34; p < 0.001) were both associated with the development of exudative AMD. The age-stratified analyses yielded similar results to the main analyses, except that the risks were exaggerated in the older part of the population. Conclusion: This is the first longitudinal nationwide study showing that both hypo- and hyperthyroidism are associated with an increased risk of exudative AMD. AMD is a quantitative problem in the population and our findings could have a public health impact. Further studies are needed to study the underlying mechanisms of the association.
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| 2. |
- Johansson, Peter, et al.
(author)
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Deep sequencing of uveal melanoma identifies a recurrent mutation in PLCB4.
- 2016
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In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:4, s. 4624-4631
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Journal article (peer-reviewed)abstract
- Next generation sequencing of uveal melanoma (UM) samples has identified a number of recurrent oncogenic or loss-of-function mutations in key driver genes including: GNAQ, GNA11, EIF1AX, SF3B1 and BAP1. To search for additional driver mutations in this tumor type we carried out whole-genome or whole-exome sequencing of 28 tumors or primary cell lines. These samples have a low mutation burden, with a mean of 10.6 protein changing mutations per sample (range 0 to 53). As expected for these sun-shielded melanomas the mutation spectrum was not consistent with an ultraviolet radiation signature, instead, a BRCA mutation signature predominated. In addition to mutations in the known UM driver genes, we found a recurrent mutation in PLCB4 (c.G1888T, p.D630Y, NM_000933), which was validated using Sanger sequencing. The identical mutation was also found in published UM sequence data (1 of 56 tumors), supporting its role as a novel driver mutation in UM. PLCB4 p.D630Y mutations are mutually exclusive with mutations in GNA11 and GNAQ, consistent with PLCB4 being the canonical downstream target of the former gene products. Taken together these data suggest that the PLCB4 hotspot mutation is similarly a gain-of-function mutation leading to activation of the same signaling pathway, promoting UM tumorigenesis.
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| 3. |
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| 4. |
- Mandal, Nakul, et al.
(author)
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Proteomic Analysis of the Vitreous following Experimental Retinal Detachment in Rabbits.
- 2015
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In: Journal of Ophthalmology. - : Hindawi Limited. - 2090-0058 .- 2090-004X. ; 2015
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Journal article (peer-reviewed)abstract
- Purpose. The pathogenesis of rhegmatogenous retinal detachment (RRD) remains incompletely understood, with no clinically effective treatment for potentially severe complications such as photoreceptor cell death and proliferative vitreoretinopathy. Here we investigate the protein profile of the vitreous following experimental retinal detachment using a comparative proteomic based approach. Materials and Methods. Retinal detachment was created in the right eyes of six New Zealand red pigmented rabbits. Sham surgery was undertaken in five other rabbits that were used as controls. After seven days the eyes were enucleated and the vitreous was removed. The vitreous samples were evaluated with two-dimensional polyacrylamide gel electrophoresis and the differentially expressed proteins were identified with tandem mass spectrometry. Results. Ten protein spots were found to be at least twofold differentially expressed when comparing the vitreous samples of the sham and retinal detachment surgery groups. Protein spots that were upregulated in the vitreous following retinal detachment were identified as albumin fragments, and those downregulated were found to be peroxiredoxin 2, collagen-Iα1 fragment, and α-1-antiproteinase F. Conclusions. Proteomic investigation of the rabbit vitreous has identified a set of proteins that help further our understanding of the pathogenesis of rhegmatogenous retinal detachment and its complications.
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| 5. |
- Sjo, Nicolai C., et al.
(author)
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Role of Helicobacter pylori in conjunctival mucosa-associated lymphoid tissue lymphoma
- 2007
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In: Ophthalmology. - : Elsevier BV. - 1549-4713 .- 0161-6420. ; 114:1, s. 182-186
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Journal article (peer-reviewed)abstract
- Objective: Conjunctiva-associated lymphoid tissue is the conjunctival equivalent to mucosa-associated lymphoid tissue (MALT). Mucosa-associated lymphoid tissue lymphoma has been shown to be associated with Helicobacter pylori. In this study, the prevalence and possible role of H. pylori infection in conjunctival MALT lymphoma were evaluated. Design: Retrospective noncomparative case series. Participants: Thirteen cases of conjunctival MALT lymphoma were investigated. Five samples of conjunctival lymphoid hyperplasia and 20 biopsies of normal conjunctiva served as controls. Methods: The specimens were investigated for the presence of H. pylori with immunohistochemistry (IHC) and nested polymerase chain reaction (PCR) techniques. For each case of conjunctival MALT lymphoma, information regarding gender, age at presentation, conjunctival localization, and information of generalized MALT lymphoma were collected. Main Outcome Measures: Detection of H. pylori and patient characteristics. Results: The 13 conjunctival MALT lymphomas originated from 8 women and 5 men with an average age of 62 years (range, 25-87). Only 1 patient had evidence of systemic MALT lymphoma. H. pylon could not be identified in any of the conjunctival MALT lymphomas, in conjunctival lymphoid hyperplasia, or in normal conjunctival biopsies using IHC and PCR techniques. Conclusions: An association between H. pylori and localized conjunctival MALT lymphoma could not be verified. Antigens other than H. pylon may take part in the development of conjunctival MALT lymphoma.
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| 6. |
- Stenman, Lisa, et al.
(author)
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Primary orbital precursor T-cell lymphoblastic lymphoma: Report of a unique case.
- 2016
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In: Molecular and clinical oncology. - : Spandidos Publications. - 2049-9450 .- 2049-9469. ; 5:5, s. 593-595
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Journal article (peer-reviewed)abstract
- Primary T-cell lymphoblastic lymphoma (T-LBL) in the eye region is very rare. The present study described a unique case of T-LBL involving the extraocular muscles. A 22-year-old male patient presented with a 3-week history of headache, reduced visual acuity and edema of the left eye. Clinical examination revealed left-sided exophthalmus, periorbital edema, chemosis, and reduced motility of the left eye. A magnetic resonance imaging scan revealed thickening of the left orbital muscles and a positron emission tomography-computed tomography scan also demonstrated activity in a subclavicular lymph node. Histopathological analysis of both lesions revealed infiltration by medium-sized neoplastic lymphoid cells with a high nuclear-cytoplasmic ratio and a high mitotic index. Immunostaining revealed positivity for CD2, CD3, CD99, Tia-1, and GranzymB, and variable positivity for CD4. There was no involvement of the bone marrow. Based on the clinical and histopathological findings, a diagnosis of T-LBL was made. There was no evidence of NOTCH1 mutation or rearrangements of the ETV6 and MLL genes and high-resolution array-based comparative genomic hybridization (arrayCGH) analysis revealed a normal genomic profile. The patient received chemotherapy according to the high-risk NOPHO protocol, followed by myeloablative allogenic bone marrow transplantation. At 35 months after diagnosis, the patient remained in complete first remission, but without light perception on his left eye. To the best of our knowledge, this is the first report of a case of T-LBL involving the extraocular muscles. Although primary T-LBL in the eye region is very rare, our findings demonstrate that lymphoma should be considered in the differential diagnosis of patients with similar symptoms.
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| 7. |
- Thyssen, Jacob P., et al.
(author)
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Management of ocular manifestations of atopic dermatitis : A consensus meeting using a modified delphi process
- 2020
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In: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 0001-5555 .- 1651-2057. ; 100:16
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Journal article (peer-reviewed)abstract
- There is a need for unified guidance on the management of ocular manifestations of atopic dermatitis and ocular manifestations associated with dupilumab in the Nordic region (Denmark, Finland, Norway and Sweden). This initiative gathered Nordic dermatologists and ophthalmologists to identify consensus in this area using a modified Delphi process. The initiative was led by a Nordic expert panel who developed a questionnaire that was circulated to a wider group. The results informed an agenda consisting of 24 statements to be voted on using a 5-point Likert scale at a meeting in Copenhagen on 24 April 2019. A facilitator moderated discussion and revised statements according to expert feedback for a second vote when required to reach consensus. Consensus was reached for 23 statements regarding the diagnosis, treatment and referral of these patients, which we hope will improve patient management in the Nordic region.
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| 8. |
- von Holstein, Sarah Linéa, et al.
(author)
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CRTC1-MAML2 gene fusion in mucoepidermoid carcinoma of the lacrimal gland.
- 2012
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In: Oncology reports. - : Spandidos Publications. - 1791-2431 .- 1021-335X. ; 27:5, s. 1413-6
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Journal article (peer-reviewed)abstract
- Epithelial tumors of the lacrimal gland are histologically similar to salivary gland tumors. Here we report on a rare case of mucoepidermoid carcinoma (MEC) in a 73‑year-old man with a swelling of the left lacrimal gland. The tumor had a microscopic appearance consistent with a classical low-grade MEC of the lacrimal gland. There were no signs of recurrence or metastases during a five-year follow-up. Using RT-PCR and FISH we demonstrated that the tumor was positive for the CRTC1-MAML2 gene fusion previously shown to be associated with in particular low-grade salivary MECs with favorable prognosis. By immunohistochemistry we showed that the majority of tumor cells, including epidermoid, intermediate and mucous producing cells, expressed the CRTC1-MAML2 fusion protein. In contrast, 15 non-MEC lacrimal neoplasm were fusion-negative. Our findings show that lacrimal MEC is not only clinically and morphologically but also genetically identical to MECs originating from other exocrine glands, including those of the lung, thyroid, cervix and salivary glands. Taken together, the present and previous studies further emphasize the fundamental biologic and genetic similarities among MECs developing from different anatomical sites and organs. Moreover, our findings indicate that the CRTC1-MAML2 fusion may be a useful diagnostic and prognostic biomarker for lacrimal MEC.
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| 9. |
- von Holstein, Sarah Linéa, et al.
(author)
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Lacrimal gland lesions in Denmark between 1974 and 2007.
- 2013
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In: Acta ophthalmologica. - : Wiley. - 1755-3768 .- 1755-375X. ; 91:4, s. 349-354
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Journal article (peer-reviewed)abstract
- Purpose: To evaluate the incidence rate, distribution, patient characteristics and indications for surgical intervention of lacrimal gland lesions in Denmark between 1974 and 2007. Material and methods: All biopsied/surgically removed lacrimal gland lesions in Denmark during the period 1974-2007 were identified by searching two population-based registries. Specimens were collected and re-evaluated. The following data were collected: age, gender, indications for surgical intervention and local recurrence. Results: A total of 232 lesions from 210 patients with a histologically verified lesion of the lacrimal gland were included. The incidence rate of lacrimal gland lesions was 1.3/1000000/year. The overall annual age- and gender-adjusted incidence rate more than doubled during the study period, owing to an increase in non-malignant lesions. Approximately half of the lesions were neoplasms (119) and 55% (66) of these were malignant. Dacryops constituted 10% (24), inflammatory lesions 27% (62), normal tissue 12% (27), benign tumours 23% (53) and malignant tumours 29% (66). Patients with malignant neoplasms were significantly older than patients with benign neoplasms (63 versus 48years, p<0.001). The indication for surgical intervention was suspicion of a tumour in more than 90% of the neoplastic lesions and in 30% of the non-neoplastic lesions. Conclusion: Lacrimal gland lesions that require surgical evaluation are rare in the Danish population and represent a wide spectrum of diagnoses, mostly benign. The overall incidence rate of biopsied lacrimal gland lesions is increasing.
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| 10. |
- Wadt, Karin A W, et al.
(author)
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Molecular characterization of melanoma cases in denmark suspected of genetic predisposition.
- 2015
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:3
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Journal article (peer-reviewed)abstract
- Both environmental and host factors influence risk of cutaneous melanoma (CM), and worldwide, the incidence varies depending on constitutional determinants of skin type and pigmentation, latitude, and patterns of sun exposure. We performed genetic analysis of CDKN2A, CDK4, BAP1, MC1R, and MITFp.E318K in Danish high-risk melanoma cases and found CDKN2A germline mutations in 11.3% of CM families with three or more affected individuals, including four previously undescribed mutations. Rare mutations were also seen in CDK4 and BAP1, while MC1R variants were common, occurring at more than twice the frequency compared to Danish controls. The MITF p.E318K variant similarly occurred at an approximately three-fold higher frequency in melanoma cases than controls. To conclude, we propose that mutation screening of CDKN2A and CDK4 in Denmark should predominantly be performed in families with at least 3 cases of CM. In addition, we recommend that testing of BAP1 should not be conducted routinely in CM families but should be reserved for families with CM and uveal melanoma, or mesothelioma.
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