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  1. Article ; Online: Keratitis fugax hereditaria: hiding in plain sight in Sweden?

    Kivelä, Tero T

    Acta ophthalmologica

    2022  Volume 100, Issue 6, Page(s) 603–604

    MeSH term(s) Humans ; Keratitis/congenital ; Keratitis/diagnosis ; Sweden/epidemiology
    Language English
    Publishing date 2022-08-10
    Publishing country England
    Document type Editorial
    ZDB-ID 2408333-1
    ISSN 1755-3768 ; 1755-375X
    ISSN (online) 1755-3768
    ISSN 1755-375X
    DOI 10.1111/aos.15064
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Beware of Polymegathism.

    Kivelä, Tero T

    Cornea

    2021  Volume 40, Issue 7, Page(s) e15

    MeSH term(s) Cell Size ; Endothelium, Corneal/pathology ; Eye Diseases, Hereditary/pathology ; Genetic Diseases, X-Linked/pathology ; Humans ; Ophthalmology ; Societies, Medical ; Terminology as Topic
    Language English
    Publishing date 2021-03-25
    Publishing country United States
    Document type Letter
    ZDB-ID 604826-2
    ISSN 1536-4798 ; 0277-3740
    ISSN (online) 1536-4798
    ISSN 0277-3740
    DOI 10.1097/ICO.0000000000002732
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Clinical and Histopathologic Characteristics and Template of the TGFBI p.(His626Arg) Missense Variant Lattice Corneal Dystrophy.

    Jaakkola, Aino M / Kivelä, Tero T

    Cornea

    2023  Volume 42, Issue 9, Page(s) 1124–1132

    Abstract: Purpose: The aim of this study was to define, following the IC3D template format, the clinical and histopathologic phenotype of the p.(His626Arg) missense variant lattice corneal dystrophy (LCDV-H626R), the most common variant lattice dystrophy, and to ... ...

    Abstract Purpose: The aim of this study was to define, following the IC3D template format, the clinical and histopathologic phenotype of the p.(His626Arg) missense variant lattice corneal dystrophy (LCDV-H626R), the most common variant lattice dystrophy, and to record long-term outcome of corneal transplantation in this dystrophy.
    Methods: A database search and a meta-analysis of published data on LCDV-H626R were conducted. A patient diagnosed with LCDV-H626R who underwent bilateral lamellar keratoplasty followed by rekeratoplasty of 1 eye is described, including histopathologic examination of the 3 keratoplasty specimens.
    Results: One hundred forty-five patients from at least 61 families and 11 countries diagnosed with LCDV-H626R were found. This dystrophy is characterized by recurrent erosions, asymmetric progression, and thick lattice lines that extend to corneal periphery. The median age is 37 (range, 25-59) years at the onset of symptoms, 45 (range, 26-62) years at the time of diagnosis, and 50 (range, 41-78) years at the time of the first keratoplasty, suggesting a median interval from the first symptoms to diagnosis and to keratoplasty of 7 and 12 years, respectively. Clinically unaffected carriers have been of age 6 to 45 years. Central anterior stromal haze and centrally thick, peripherally thinner branching lattice lines in the anterior to midstroma of the cornea were noted preoperatively. Histopathology of the host anterior corneal lamella showed a subepithelial fibrous pannus, a destroyed Bowman layer, and amyloid deposits extending to the deep stroma. In the rekeratoplasty specimen, amyloid localized to scarring along the Bowman membrane and to the margins of the graft.
    Conclusions: The IC3D-type template for LCDV-H626R should help diagnose and manage variant carriers. The histopathologic spectrum of findings is broader and more nuanced than what has been reported.
    MeSH term(s) Humans ; Amyloid Neuropathies, Familial ; Cornea/pathology ; Corneal Dystrophies, Hereditary/diagnosis ; Corneal Dystrophies, Hereditary/genetics ; Corneal Dystrophies, Hereditary/surgery ; Corneal Transplantation ; Extracellular Matrix Proteins/genetics ; Mutation, Missense ; Transforming Growth Factor beta/genetics
    Chemical Substances Extracellular Matrix Proteins ; Transforming Growth Factor beta ; betaIG-H3 protein (148710-76-3)
    Language English
    Publishing date 2023-02-10
    Publishing country United States
    Document type Meta-Analysis ; Journal Article
    ZDB-ID 604826-2
    ISSN 1536-4798 ; 0277-3740
    ISSN (online) 1536-4798
    ISSN 0277-3740
    DOI 10.1097/ICO.0000000000003247
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  4. Article ; Online: Functional assay for assessment of pathogenicity of BAP1 variants.

    Repo, Pauliina E / Backlund, Michael P / Kivelä, Tero T / Turunen, Joni A

    Human molecular genetics

    2024  Volume 33, Issue 5, Page(s) 426–434

    Abstract: Background: Pathogenic germline variants in BRCA1-Associated Protein 1 (BAP1) cause BAP1 tumor predisposition syndrome (BAP1-TPDS). Carriers run especially a risk of uveal (UM) and cutaneous melanoma, malignant mesothelioma, and clear cell renal ... ...

    Abstract Background: Pathogenic germline variants in BRCA1-Associated Protein 1 (BAP1) cause BAP1 tumor predisposition syndrome (BAP1-TPDS). Carriers run especially a risk of uveal (UM) and cutaneous melanoma, malignant mesothelioma, and clear cell renal carcinoma. Approximately half of increasingly reported BAP1 variants lack accurate classification. Correct interpretation of pathogenicity can improve prognosis of the patients through tumor screening with better understanding of BAP1-TPDS.
    Methods: We edited five rare BAP1 variants with differing functional characteristics identified from patients with UM in HAP1 cells using CRISPR-Cas9 and assayed their effect on cell adhesion/spreading (at 4 h) and proliferation (at 48 h), measured as cell index (CI), using xCELLigence real-time analysis system.
    Results: In BAP1 knockout HAP1 cultures, cell number was half of wild type (WT) cultures at 48 h (p = 0.00021), reaching confluence later, and CI was 78% reduced (p < 0.0001). BAP1-TPDS-associated null variants c.67+1G>T and c.1780_1781insT, and a likely pathogenic missense variant c.281A>G reduced adhesion (all p ≤ 0.015) and proliferation by 74%-83% (all p ≤ 0.032). Another likely pathogenic missense variant c.680G>A reduced both by at least 50% (all p ≤ 0.032), whereas cells edited with likely benign one c.1526C>T grew similarly to WT.
    Conclusions: BAP1 is essential for optimal fitness of HAP1 cells. Pathogenic and likely pathogenic BAP1 variants reduced cell fitness, reflected in adhesion/spreading and proliferation properties. Further, moderate effects were quantifiable. Variant modelling in HAP1 with CRISPR-Cas9 enabled functional analysis of coding and non-coding region variants in an endogenous expression system.
    MeSH term(s) Humans ; Melanoma/pathology ; Skin Neoplasms ; Virulence ; Genetic Predisposition to Disease ; Uveal Neoplasms ; Germ-Line Mutation/genetics ; Ubiquitin Thiolesterase/genetics ; Ubiquitin Thiolesterase/metabolism ; Kidney Neoplasms ; Tumor Suppressor Proteins/genetics
    Chemical Substances Ubiquitin Thiolesterase (EC 3.4.19.12) ; BAP1 protein, human ; Tumor Suppressor Proteins
    Language English
    Publishing date 2024-01-08
    Publishing country England
    Document type Journal Article
    ZDB-ID 1108742-0
    ISSN 1460-2083 ; 0964-6906
    ISSN (online) 1460-2083
    ISSN 0964-6906
    DOI 10.1093/hmg/ddad193
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Histopathology of Exfoliation Syndrome.

    Kivelä, Tero T

    Journal of glaucoma

    2018  Volume 27 Suppl 1, Page(s) S38–S43

    Abstract: Exfoliation syndrome (XFS) is characterized by light and electron microscopy by age-dependent gradual accumulation of whitish material of largely unknown composition and origin along both the anterior and posterior chambers and widely within the iris ... ...

    Abstract Exfoliation syndrome (XFS) is characterized by light and electron microscopy by age-dependent gradual accumulation of whitish material of largely unknown composition and origin along both the anterior and posterior chambers and widely within the iris stroma. These deposits can be fairly specifically labeled with selected antibodies and lectins. Immunohistochemistry shows that intraocular exfoliation deposits share antigens with the microfibrillar elastic fiber system and several basement membrane components, including carbohydrate epitopes on glycosaminoglycans, proteoglycans, and cell adhesion molecules. The earliest histopathologic manifestation of XFS seems to be the deposition of characteristic fibers in various extraocular and anterior segment tissues, as observed by electron microscopy, and perivascular deposition of material within the iris stroma, which is antigenically typical of that found in classic intraocular exfoliation deposits. These findings precede the clinical diagnosis of XFS and likewise can be detected in the seemingly uninvolved fellow eyes of patients with clinically unilateral XFS. Indeed, histopathologic examination of capsulotomy, iridectomy, and trabeculectomy specimens can lead to a clinically unexpected diagnosis of XFS. Exfoliation fibers are additionally found widely distributed in extraocular connective tissues and visceral organs, but the matrix of these fibers seems to differ from that of intraocular deposits. In addition to this histopathologic discrepancy, both the frequent occurrence of clinically unilateral, histopathologically highly asymmetric exfoliation deposits, and the relationship between the early iris vasculopathy that not infrequently may be observed histopathologically for years before classic widespread exfoliation deposits appear along the anterior and posterior chambers remain to be resolved.
    MeSH term(s) Anterior Eye Segment/pathology ; Elastic Tissue/pathology ; Exfoliation Syndrome/pathology ; Glaucoma, Open-Angle/pathology ; Humans ; Intraocular Pressure ; Trabeculectomy
    Language English
    Publishing date 2018-03-10
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 913494-3
    ISSN 1536-481X ; 1057-0829
    ISSN (online) 1536-481X
    ISSN 1057-0829
    DOI 10.1097/IJG.0000000000000947
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: The first description of the complete natural history of uveal melanoma by two Scottish surgeons, Allan Burns and James Wardrop.

    Kivelä, Tero T

    Acta ophthalmologica

    2017  

    Abstract: James Wardrop (1782-1869), a young Scottish surgeon and an early ophthalmologist in Edinburgh, is credited for describing in 1809 retinoblastoma as an entity in his treatise 'Observations on Fungus Haematodes or Soft Cancer'. His treatise also reveals ... ...

    Abstract James Wardrop (1782-1869), a young Scottish surgeon and an early ophthalmologist in Edinburgh, is credited for describing in 1809 retinoblastoma as an entity in his treatise 'Observations on Fungus Haematodes or Soft Cancer'. His treatise also reveals that Allan Burns (1781-1813), another young Scottish surgeon and anatomist, had invited Wardrop to assist in enucleating an eye from a 41-year-old Glasgow woman who, in retrospect, had a uveal melanoma. Her eye had become blind 4 months after symptoms of exudative retinal detachment had appeared, and it had become painful after a further 2-4 months. The tumour eventually perforated the sclera, and she died within a year thereafter of hepatic metastases. Burns and Wardrop went on to publish detailed parallel accounts of the symptoms, signs, ophthalmic pathology and post-mortem findings regarding the primary, recurrent and metastatic tumour. Burns may have performed the post-mortem after exhuming the body, a common occurrence in early 19th Century Scotland, a thriving hub for teaching morbid anatomy to young surgeons at the time.
    Language English
    Publishing date 2017-08-21
    Publishing country England
    Document type Journal Article
    ZDB-ID 2408333-1
    ISSN 1755-3768 ; 1755-375X
    ISSN (online) 1755-3768
    ISSN 1755-375X
    DOI 10.1111/aos.13535
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Incidence and Risk Factors for Secondary Glaucoma in Eyes with Uveal Melanoma.

    Stadigh, Anni E / Puska, Päivi M / Kivelä, Tero T

    Ophthalmology. Glaucoma

    2022  Volume 6, Issue 1, Page(s) 29–41

    Abstract: Purpose: To estimate incidence of and analyze risk factors for developing secondary glaucoma in eyes with uveal melanoma before and after diagnosis.: Design: A cross-sectional, population-based cohort study.: Participants: Seven hundred eighty-one ...

    Abstract Purpose: To estimate incidence of and analyze risk factors for developing secondary glaucoma in eyes with uveal melanoma before and after diagnosis.
    Design: A cross-sectional, population-based cohort study.
    Participants: Seven hundred eighty-one patients (median age, 64 years; range, 14-93) consecutively diagnosed with uveal melanoma from 1997 to 2012 in a national ocular oncology service, 708 (91%) of whom received ruthenium (50%) or iodine (50%) brachytherapy.
    Methods: Patient, tumor, treatment, and follow-up data were collected prospectively. Frequency and associations of melanoma-related glaucoma at tumor diagnosis were assessed. Incidence of developing secondary glaucoma after diagnosis was estimated by Kaplan-Meier analysis. Independent risk factors were modeled using Cox regression.
    Main outcome measures: Melanoma-related glaucoma and related risk factors.
    Results: Forty-five patients (5.8%; 95% confidence interval [CI], 4.2-7.6) had tumor-related secondary glaucoma at diagnosis, 34 (76%) from a narrow-to-closed angle (25 had direct angle invasion) and 10 (22%) from anterior neovascularization. Synchronous metastases were common in patients with initial secondary glaucoma (11% vs. 1.2% with incident glaucoma, P = 0.005). Patients with secondary glaucoma were often male (58% vs. 48% without glaucoma; P = 0.010) and had larger tumors (median thickness, 9.1 vs. 4.0 mm; P < 0.001) involving the ciliary body (43% vs. 21%; P < 0.001) with retinal detachment (53% vs. 30%; P < 0.001). One hundred and sixty-eight patients 165 of which were treated with brachytherapy developed incident tumor- or treatment-related secondary glaucoma a median of 1.7 years (range, 0.1-13.6) after tumor diagnosis. Cumulative proportion of developing secondary glaucoma was 23% (95% CI, 20-27) at 5 years. The most common mechanism was neovascularization in 119 patients (71%; 95% CI, 63-78). By multivariable regression, initial retinal detachment 3 to 4 quadrants (hazard ratio [HR], 2.18; P < 0.001), initial intraocular pressure 17 mmHg or higher (HR, 1.64; P = 0.01), and tumor thickness predicted incident secondary glaucoma.
    Conclusions: Secondary glaucoma at initial uveal melanoma diagnosis predicts high risk of synchronous metastases. Although anterior neovascularization is the most common mechanism for secondary glaucoma after diagnosis, other mechanisms such as angle narrowing and anterior chamber hemorrhage are not infrequent. Initial retinal detachment and intraocular pressure with tumor thickness could inform interim assessments of intraocular pressure and neovascularization.
    MeSH term(s) Humans ; Male ; Middle Aged ; Retinal Detachment ; Incidence ; Cohort Studies ; Cross-Sectional Studies ; Glaucoma/diagnosis ; Glaucoma/epidemiology ; Glaucoma/etiology ; Uveal Neoplasms/complications ; Uveal Neoplasms/diagnosis ; Uveal Neoplasms/epidemiology ; Melanoma/complications ; Melanoma/diagnosis ; Melanoma/epidemiology ; Risk Factors
    Language English
    Publishing date 2022-08-12
    Publishing country United States
    Document type Journal Article
    ISSN 2589-4196
    ISSN (online) 2589-4196
    DOI 10.1016/j.ogla.2022.08.002
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  8. Article ; Online: Trends in Keratoplasty Procedures During 2 Decades in a Major Tertiary Referral Center in Finland: 1995 to 2015.

    Ala-Fossi, Olli / Krootila, Kari / Kivelä, Tero T

    Cornea

    2022  Volume 42, Issue 1, Page(s) 36–43

    Abstract: Purpose: The purpose of this study was to analyze trends in number, age-adjusted frequency, and type of keratoplasty in a major tertiary referral center, relative to patient and graft characteristics.: Methods: A retrospective registry study of 1574 ... ...

    Abstract Purpose: The purpose of this study was to analyze trends in number, age-adjusted frequency, and type of keratoplasty in a major tertiary referral center, relative to patient and graft characteristics.
    Methods: A retrospective registry study of 1574 patients who in 1995 to 2015 underwent keratoplasty in the Helsinki University Eye Hospital (HUEH). Graft type and sequence, patient characteristics, and date of surgery were recorded. Main outcome measures were annual number, type, and age-adjusted frequency of keratoplasty; patient and graft characteristics; graft procurement; and national population-adjusted frequency of keratoplasty.
    Results: In HUEH, from 1995 to 2015, a total of 2191 keratoplasties were performed with 48% of the grafts procured intramurally; 76% were primary and 24% regrafts. The age-adjusted frequency of primary penetrating keratoplasty decreased by 52% from 0.96 to 0.46 per 100,000. The corresponding frequency of primary Descemet stripping automated endothelial keratoplasty increased by 367% from 0.3 to 1.4 after 2006, finally accounting for 68% of primary grafts. Men underwent primary penetrating keratoplasty (median 48 vs. 67 yrs, P = 0.0001) and anterior lamellar keratoplasty (median 37 vs. 46 yrs, P = 0.0015) at a younger age than women. Interval to the first regraft was comparable between sexes (median 2.2 vs. 1.9 yrs, respectively, P = 0.17). The national median population-adjusted frequency of keratoplasties was 3.2 per 100,000 from 2009 to 2015, and HUEH accounted for a median of 69% of them.
    Conclusions: The increased frequency of keratoplasty in HUEH resulted from rapid adoption of Descemet stripping automated endothelial keratoplasty after 2006 and was facilitated by centralizing graft procurement to HUEH and the National Cell and Tissue Center Regea.
    MeSH term(s) Male ; Humans ; Female ; Tertiary Care Centers ; Finland/epidemiology ; Retrospective Studies ; Corneal Transplantation ; Keratoplasty, Penetrating
    Language English
    Publishing date 2022-01-25
    Publishing country United States
    Document type Journal Article
    ZDB-ID 604826-2
    ISSN 1536-4798 ; 0277-3740
    ISSN (online) 1536-4798
    ISSN 0277-3740
    DOI 10.1097/ICO.0000000000002990
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  9. Article ; Online: Intravenous hypertonic saline to reduce intraocular pressure: the effect of splitting the bolus.

    Inborr, Pia / Harju, Mika / Kivelä, Tero T

    Acta ophthalmologica

    2022  Volume 100, Issue 8, Page(s) e1606–e1610

    Abstract: Purpose: To compare intraocular pressure (IOP) and pain after a single versus split bolus of intravenous hypertonic saline (IVHTS).: Methods: In a prospective, randomized, interventional trial, we enrolled patients with an IOP of 22-34 mmHg. Twenty ... ...

    Abstract Purpose: To compare intraocular pressure (IOP) and pain after a single versus split bolus of intravenous hypertonic saline (IVHTS).
    Methods: In a prospective, randomized, interventional trial, we enrolled patients with an IOP of 22-34 mmHg. Twenty patients in Group 1 received IVHTS as a single bolus of 1 mmol/kg 23.4% sodium chloride, and 13 patients in Group 2 received two boli of 0.5 mmol/kg separated by 10 min. They graded pain at the infusion site. We measured IOP, heart rate and blood pressure before and 10 and 20 min after IVHTS.
    Results: Eighteen patients (90%) in Group 1 felt pain (median, 6.5; range, 0-10). In Group 2, 11 patients (85%) felt pain after the first bolus (median, 6.0; range, 0-8) and 12 (92%) after the second one (median, 8; range, 0-10). We found no difference in pain grade between the groups after their first bolus (p = 0.33) or between the first bolus of Group 1 and the second bolus of Group 2 (p = 0.47). The median IOP reduction in Group 1 was 6.5 mmHg (range, 2-16) at 10 min and 7.0 mmHg (range, 4-16) at 20 min (p < 0.001 for both). In Group 2, the corresponding reductions after the second bolus were 9.0 mmHg (range, 4-10; p = 0.002) and 8.0 mmHg (range, 6-11; p = 0.002). The IOP reduction at 10 and 20 min was comparable between groups (p = 0.094 and p = 0.41, respectively).
    Conclusion: Splitting the bolus did not reduce pain associated with IVHTS. Single bolus is consequently recommended.
    MeSH term(s) Humans ; Intraocular Pressure ; Prospective Studies ; Tonometry, Ocular ; Glaucoma, Open-Angle ; Pain
    Language English
    Publishing date 2022-03-29
    Publishing country England
    Document type Randomized Controlled Trial ; Journal Article
    ZDB-ID 2408333-1
    ISSN 1755-3768 ; 1755-375X
    ISSN (online) 1755-3768
    ISSN 1755-375X
    DOI 10.1111/aos.15139
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  10. Article ; Online: Letter to the editor: Keratitis fugax hereditaria is an eye-specific cryopyrin-associated periodic syndrome.

    Turunen, Joni A / Immonen, Annamari T / Kivelä, Tero T

    Autoimmunity reviews

    2022  Volume 21, Issue 7, Page(s) 103054

    MeSH term(s) Cryopyrin-Associated Periodic Syndromes/complications ; Cryopyrin-Associated Periodic Syndromes/diagnosis ; Cryopyrin-Associated Periodic Syndromes/genetics ; Humans ; Keratitis/congenital ; Keratitis/diagnosis ; Keratitis/genetics ; NLR Family, Pyrin Domain-Containing 3 Protein
    Chemical Substances NLR Family, Pyrin Domain-Containing 3 Protein
    Language English
    Publishing date 2022-01-26
    Publishing country Netherlands
    Document type Letter ; Comment
    ZDB-ID 2144145-5
    ISSN 1873-0183 ; 1568-9972
    ISSN (online) 1873-0183
    ISSN 1568-9972
    DOI 10.1016/j.autrev.2022.103054
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