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Biomedical subjects

Tero Kivelä

Publications and source records attributed to Tero Kivelä.

At least 19 recordsLinked to original sources
PubMed2006

Transscleral local resection versus iodine brachytherapy for uveal melanomas that are large because of tumour height.

BACKGROUND: To compare visual outcome and ocular complications of transscleral local resection (TSR) with those of iodine-125 plaque brachytherapy (IBT) for uveal melanomas categorised as large because of tumour height. METHODS: Retrospective study of 87 patients with a uveal melanoma <or=16 mm by largest basal diameter (median, 12.6 vs 14.0 mm for TSR and IBT, respectively) and large by height (median, 11.0 vs 10.6 mm) by the Collaborative Ocular Melanoma Study (COMS) criteria. Thirty-three patients underwent TSR in the United Kingdom and 54 underwent IBT in Finland. Loss of 20/65 and 20/400 vision, local tumour recurrence, cataract, iris neovascularization, glaucoma, maculopathy, optic neuropathy, persistent retinal detachment, and vitreous haemorrhage were analysed using competing risks and logistic regression to control for confounders. RESULTS: All patients save one managed with TSR lost 20/70 vision within 3 years. The 2-year cumulative incidence of losing 20/400 vision was 60% (95% CI, 35-75) for TSR and 75% (95% CI, 59-86) for IBT. The 5-year incidence of local tumour recurrence was 41% (95% CI, 17-63) after TSR and 7% (95% CI, 2-17) after IBT. Glaucoma and optic neuropathy were rare after TSR. Cataract, maculopathy, retinal detachment, and vitreous haemorrhage were common after either treatment. The number of patients needed to treat with TSR instead of IBT was four for one additional patient to benefit by avoiding loss of visual acuity 20/400 for at least 2 years, and the corresponding number was three for one additional patient to experience a local recurrence from TSR. CONCLUSIONS: If TSR is further evaluated as an alternative to IBT in avoiding blindness of an eye with a ciliochoroidal melanoma categorised as large by COMS criteria because of its height, special emphasis must be given to increased risk of local tumour recurrence.

Aged↗
PubMed2006

Pigmented episcleral deposits after brachytherapy of uveal melanoma.

PURPOSE: To describe the characteristics and evolution of pigmented episcleral deposits after brachytherapy for uveal melanoma to determine their origin and association with melanoma-related mortality. DESIGN: Noncomparative case series. PARTICIPANTS: Two hundred eleven patients (108 males, 103 females; median age, 61 years; range, 14-88 years) who were treated with a single ruthenium and iodine plaque therapy (median dose to tumor base, 475 Gy and 392 Gy, respectively) for a choroidal and ciliary body melanoma. Median tumor diameter and height were 12 mm and 5.5 mm, respectively. Eighty-eight patients were treated prospectively during the study. METHODS: The number and location of pigmented episcleral deposits were recorded under the slit lamp during each visit after brachytherapy. The association of the deposits with tumor characteristics and survival was analyzed with logistic regression and Kaplan-Meier analysis, respectively. MAIN OUTCOME MEASURES: Number and location of episcleral deposits, melanoma-related mortality. RESULTS: The pigmented episcleral deposits ranged from black and brownish spots to slightly thickened patches. Most deposits appeared within the first 6 months after brachytherapy. By 1 year, 85% (95% confidence interval, 77-93) of eyes had at least 1 deposit (median, 6). The deposits increased in number until 7 years from irradiation, and decreased with increasing distance from tumor center. An association between the number of deposits at 1 and 2 years and subsequent melanoma-related mortality could not be confirmed (P = 0.80 and P = 0.31, respectively). CONCLUSIONS: Pigmented macrophage-related episcleral deposits are found in most eyes with uveal melanoma after brachytherapy. Their association with plaque size and isotope rather than with tumor size suggests that radiation atrophy of retinal pigment epithelium and choroid in addition to tumor regression contributes to the formation of the deposits. Knowledge of their existence may save patients from unnecessary enucleation.

Adolescent↗
PubMed2006

Digital imaging in differential diagnosis of small choroidal melanoma.

BACKGROUND: To assess the role of digital imaging and a new subtraction method for differential diagnosis of choroidal nevus and small choroidal melanoma. METHODS: Of 241 consecutive patients referred to a tertiary referral center for suspected choroidal melanoma, 110 who underwent digital imaging of the ocular fundus were eligible for this study. Digital color, red-free and red light retinal images were evaluated in a randomized and masked manner and by the subtraction method for diagnosis of the fundus lesion. The reference standard was based on the combined results of ophthalmological examination, including mydriatic ophthalmoscopy, B scan ultrasonography, digital imaging and fluorescein angiography of the ocular fundus. RESULTS: Comparative use of digital color, red-free and red light imaging had 85.7% (95%CI 42.1-99.6) sensitivity, 99.0% (95%CI 94.7-99.9) specificity and 98.2% (95%CI 93.6-99.8) exact agreement versus reference standard in differentiation of small choroidal melanoma from pseudomelanoma. Direct comparison between use of digital images and the reference standard showed excellent agreement in detecting small choroidal melanoma from suspected choroidal lesions (K 0.847; 95%CI 0.639-1.0). The subtraction method was useful to show growth in four of 94 melanocytic choroidal tumors. The mean annual incidence of choroidal melanoma in Southwest Finland was 0.80 per 100.000 population. The most frequent choroidal pseudomelanomas were choroidal melanotic and amelanotic nevi, disciform lesions, congenital hypertrophy of the retinal pigment epithelium, and circumscribed choroidal hemangioma. CONCLUSIONS: Combined use of digital color, red-free and red light imaging was a suitable adjunct in differentiation of small choroidal melanoma from different pseudomelanomas. The subtraction method may reveal early growth of the melanotic choroidal tumors.

Adolescent↗
PubMed2006

KI-67 immunopositivity in choroidal and ciliary body melanoma with respect to nucleolar diameter and other prognostic factors.

PURPOSE: To study the association of cell proliferation in uveal melanoma with the mean of the 10 largest nucleoli (MLN), microvascular prognostic factors, and survival. METHODS: Population-based, retrospective cohort study of 167 choroidal and ciliary body melanomas enucleated from 1972 to 1981. Mouse monoclonal antibody Ki-67 (clone 7B11) was used to identify proliferating cells. MLN was measured from silver stained slides. Kaplan-Meier and Cox regression analysis were performed. RESULTS: The median number of Ki-67 immunopositive cells was 8 per tumor cross-section (range, 0-272) corresponding to a median of 0.30 cells/mm2. The percentage of immunopositive cells was 0.02% of all cells (range, 0-3.2). Tumors with epithelioid cells tended to have a higher percentage of immunopositive cells (p = 0.089). Ki-67 immunoreactivity, MLN, and presence of extravascular loops and networks were independent predictors of melanoma-related mortality, whereas Ki-67 immunoreactivity was not an independent predictor of mortality when presence of epithelioid cells was in the model. CONCLUSIONS: Taken together with previous data, the results of this population-based study support the theory that high cell proliferation index is associated with presence of epithelioid cells and that presence of a high cell proliferation index is associated with a higher risk of metastatic death independent of MLN, microvascular density, and presence extravascular loops and networks.

Cell Nucleolus↗
PubMed2005

The collaborative ocular melanoma study.

This review provides a summary of the main objectives, significant design features, and major findings and achievements of the Collaborative Ocular Melanoma Study (COMS). It has been written by two ophthalmic oncologists who were not part of the COMS study group; therefore, it represents an extramural view of the trial to supplement summaries published by the COMS investigators. Because the randomized design of the COMS was unique, no attempt is made to make any comparison with the results of previous non-controlled studies.

Brachytherapy↗
PubMed2005

Tumor, node, metastasis classification of malignant ciliary body and choroidal melanoma evaluation of the 6th edition and future directions.

PURPOSE: The tumor, node, metastasis classification of malignant uveal melanoma has been revised. We evaluated how the 6th edition (TNM6) improves on the previous one (TNM5). DESIGN: Population-based, retrospective, cross-sectional study. PARTICIPANTS: Two hundred eighty-nine consecutive patients who had a ciliary body and choroidal melanoma treated in the district of the Helsinki University Central Hospital, Finland, between 1962 and 1981. METHODS: Tumor dimensions, ciliary body involvement, and extraocular extension were evaluated from histopathologic sections and pathology reports. Tumors were assigned into categories and stages according to TNM6, TNM5, and 2 previously proposed size classifications. MAIN OUTCOME MEASURES: Proportion of tumors classified in each category and melanoma-specific survival by category and stage. RESULTS: Of the 289 melanomas, 5% were classified as pT1, 63% as pT2, 22% as pT3, and 7% as pT4 according to TNM6. The corresponding percentages based on TNM5 were 8%, 17%, 63%, and 10%. Of pT2 tumors in TNM6, 4% came from pT1, 65% from pT3, and 4% from pT4 category of TNM5. Of 28 melanomas with extraocular growth, 29% were classified as pT2 in TNM6 rather than pT4 in TNM5. The 10-year survival estimate was 2 percentage points lower for pT1, 7 percentage points higher for pT2, 17 percentage points lower for pT3, and 13 percentage points lower for pT4 by TNM6 compared with TNM5; TNM6 (P<0.0001) and the modified alternative size classifications (P = 0.0022 and P = 0.0026) divided tumors according to prognosis better than TNM5. The 10-year survival for stage I, II, and III tumors was 2 percentage points lower, 7 points higher, and 23 points lower by TNM6, which was not better than TNM5 in separating patients according to prognosis (P = 0.47). The alternative size classifications provided more equal categories and fitted the data set better than TNM5 regarding prognosis. CONCLUSIONS: TNM6 is an improvement over TNM5 in some, but not all, respects. Areas for development include taking into account ciliary body involvement and extraocular extension in more detail and combining into each stage tumor categories with similar rather than different prognosis. An evidence-based, multicenter approach would be beneficial.

Cause of Death↗
PubMed2005

Nordic research in ophthalmology.

Nordic ophthalmologists and vision scientists are active in many fields of eye research. This is most evident at the biannual Nordic Congress of Ophthalmology, most recently held in Malmö in June 2004. The authors here review some of the research in vision and ophthalmology presented at this meeting or published recently by Nordic scientists. This paper does not represent a comprehensive review of all Nordic research in the field, but attempts to give an overview of some of the activities underway in eye research in this part of the world.

Animals↗
PubMed2005

Exfoliation syndrome in Nordic countries: a comparative histopathological study of Danish and Finnish eyes with absolute glaucoma and uveal melanoma.

PURPOSE: To compare the frequency of exfoliation syndrome (EXS) in Denmark and Finland in eyes enucleated for absolute glaucoma and uveal melanoma and to correlate these results to reported clinical prevalence rates. METHODS: The material consisted of 304 and 39 eyes consecutively removed because of absolute glaucoma and of 240 and 149 eyes enucleated because of uveal melanoma in Denmark and Finland, respectively. Histological sections of all eyes were stained with haematoxylin-eosin and periodic acid-Schiff and examined under a light microscope for EXS. Diagnosis of EXS was made by the consensus of the investigators. RESULTS: In absolute glaucoma eyes, EXS was observed in 12 out of 304 eyes (3.9%, 95% CI 2.1-6.8) in Denmark, and in 16 out of 39 eyes (41%, 95% CI 26-58) in Finland (p < 0.0001). In the melanoma eyes, EXS was noted in two out of 240 eyes (0.8%, 95% CI 0.1-3.0) in Denmark and in nine out of 149 eyes (6.0%, 95% CI 2.8-11) (p < 0.0037) in Finland. CONCLUSIONS: The frequency of EXS was significantly higher in eyes removed for absolute glaucoma and malignant melanoma in Finland than in Denmark. This supports the clinical impression that EXS is rare in Denmark compared to other Nordic countries.

Adolescent↗
PubMed2004

Scanning laser Doppler flowmetry shows reduced retinal capillary blood flow in CADASIL.

BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a progressive systemic nonatherosclerotic angiopathy which causes ischemic strokes and vascular subcortical dementia. A cross-sectional study was performed to examine the retinal vascular caliber and blood flow in CADASIL. METHODS: Scanning laser Doppler flowmetry was used in a case-control study (11 patients and controls) of peripapillary retinal circulation. Automated full-field perfusion image analysis was used to analyze the flow data. Retinal vessel calibers were measured from retinal images acquired with scanning laser ophthalmoscopy. The caliber of the superior and inferior temporal retinal artery and vein were measured 1 and 2 mm from the disc rim, and the mean values were used for analysis. RESULTS: Retinal capillary peak systolic flow (mean, 249 versus 311 arbitrary unit [AU]; P=0.072) was lower, and mean capillary flow (mean, 184 versus 224 AU; P=0.12) and minimum diastolic flow (mean, 105 versus 132 AU; P=0.16) tended to be lower in patients than in controls. No significant difference in the calibers of proximal retinal arteries (mean, 104 versus 108 microm) and veins (mean, 150 versus 145 microm) was found between the patients and controls. CONCLUSIONS: Retinal capillary blood flow is mild to moderately reduced in CADASIL but that does not appear to cause major ischemic injury. Such reduction is analogous to that in the cerebral cortex in CADASIL patients with which retina appears to share its relative sparing from severe arterial ischemic tissue damage.

Adult↗
PubMed2004

Mitochondrial fatty acid beta-oxidation in the human eye and brain: implications for the retinopathy of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency.

The retinal pigment epithelium (RPE) and the choriocapillaris are affected early in the retinopathy associated with long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency. RPE in culture possesses the machinery needed for mitochondrial fatty acid beta-oxidation in vitro. To further elucidate pathogenesis of LCHAD retinopathy, we performed immunohistochemistry of the human eye and brain with antibodies to beta-oxidation enzymes. Human eye and brain sections were stained with antibodies to medium-chain (MCAD) and very long-chain acyl-CoA dehydrogenase (VLCAD), short-chain 3-hydroxyacyl-CoA dehydrogenase (SCHAD), and mitochondrial trifunctional protein (MTP) harboring LCHAD. Antibodies to 2-methyl-3-hydroxybutyryl-CoA dehydrogenase (MHBD) and cytochrome c oxidase subunit I (COX I) were used as a reference. VLCAD, MTP, MCAD, SCHAD, MHBD, and COX I antibodies labeled most retinal layers and tissues of the human eye actively involved in oxidative metabolism (extraocular and intraocular muscle, the RPE, the corneal endothelium, and the ciliary epithelium). MTP and COX I antibodies labeled the inner segments of photoreceptors. The choriocapillaris was labeled only with SCHAD and MCAD antibodies. In the brain, the choroid plexus and nuclei of the brain stem were most intensely labeled with beta-oxidation antibodies, whereas COX I antibodies strongly labeled neurons in several regions of the brain. Mitochondrial fatty acid beta-oxidation likely plays a role in ocular energy production in vivo. The RPE rather than the choriocapillaris could be the critical affected cell layer in LCHAD retinopathy. Reduced energy generation in the choroid plexus may contribute to the cerebral edema observed in patients with beta-oxidation defects.

3-Hydroxyacyl CoA Dehydrogenases↗