Publications by authors named "Ilkka Immonen"

48 Publications

Early middle age cholesterol levels and the association with age-related macular degeneration.

Acta Ophthalmol 2021 Feb 3. Epub 2021 Feb 3.

University of Helsinki, Helsinki, Finland.

Purpose: To examine whether serum cholesterol in early middle age is associated with age-related macular degeneration (AMD) later in life.

Methods: A group of Helsinki Businessmen Study (HBS) participants (n = 209) were recruited for the study. Total cholesterol (TC), triglyceride and body mass index (BMI) were measured at the HBS baseline visit in 1964-1973. Lipid subfractions, BMI, smoking status and statin use were recorded in 2011 and fundus photographs graded for AMD in 2005-2012. The subjects were genotyped for the main AMD risk single nucleotide polymorphisms (SNPs).

Results: TC measured at baseline 1964-1973 was significantly higher in subjects later developing intermediate or late AMD (6.67 mmol/l versus 6.20 mmol/l, p = 0.024) or with drusen size of ≥125 µm (6.68 mmol/l versus 6.21 mmol/l, p = 0.030) compared with the rest of the study population. TC, LDL and TG values at follow-up 2011 were lower in subjects with AMD compared to those without, whereas HDL levels showed no difference. In multivariate analysis, baseline TC associated with intermediate or late AMD (OR 1.59, p = 0.004) and drusen size ≥ 125 µm (OR 1.57, p = 0.006) when corrected for age, BMI, AMD risk SNPs and smoking. Lipid values measured 2011 had no associations after correction.

Conclusions: High systemic total cholesterol in early middle age may have a role in the initial development of AMD, especially in patients later developing large drusen.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/aos.14774DOI Listing
February 2021

Outcomes of intraocular lens scleral fixation with the friction knot technique.

Acta Ophthalmol 2019 Jun 8;97(4):e506-e513. Epub 2018 Oct 8.

Vitreoretinal Surgery Unit, Department of Ophthalmology, Helsinki University Hospital, Helsinki, Finland.

Purpose: To examine the clinical outcomes of intraocular lens (IOL) scleral fixation with the friction knot technique.

Methods: Retrospective case series of 152 eyes of 152 patients with inadequate capsular bag support operated with the friction knot IOL scleral fixation technique by a single surgeon. The fixated IOLs were one-piece or three-piece models all with open loop haptics. Main outcome measures were change in corrected distance visual acuity (CDVA) and postoperative complications.

Results: The mean follow-up time was 11.7 months (median 4.9, range 0.7-64.8). The mean logarithm of the minimum angle of resolution CDVA improved from preoperative 0.77 ± 0.73 (Snellen 20/118 ± 7.3 lines) to 0.44 ± 0.56 (Snellen 20/55 ± 5.6 lines) at the final visit (p < 0.001). The main postoperative complications were ocular hypertension (30.3%), uveitis-glaucoma-hyphaema syndrome (12.5%; UGHS), vitreous haemorrhage (11.2%) and retinal detachment (8.6%). Two (1.3%) cases of suture breakage were seen. In multivariate Cox regression analysis, age under 60 years [hazard ratio (HR) = 5.41; 95% confidence interval (CI) 1.95-15.01] and scleral fixated one-piece IOL (HR = 4.23; 95% CI 1.44-12.44) were found as significant independent risk factors for developing new UGHS.

Conclusion: The friction knot technique provides a firm scleral fixation. Scleral fixation may successfully be utilized in dislocated three-piece IOLs with loop haptics. We recommend avoiding scleral fixation of one-piece IOLs in young patients due to a high risk of UGHS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/aos.13931DOI Listing
June 2019

Fluocinolone acetonide intravitreal implant (Retisert ) in the treatment of sight threatening macular oedema of juvenile idiopathic arthritis-related uveitis.

Acta Ophthalmol 2018 Sep 14;96(6):648-651. Epub 2018 Apr 14.

Department of Ophthalmology, Helsinki University Hospital, Helsinki, Finland.

Purpose: We describe eight patients with juvenile idiopathic arthritis-related chronic uveitis, who received a fluocinolone acetonide implant (FAI, Retisert®, Bausch&Lomb) in one eye. All patients had poor visual acuity (VA) due to persistent macular oedema in one or both eyes despite treatment with antirheumatic medication.

Methods: Median age of the patients was 22.9 years (range, 14.1-39.7) and duration of uveitis 13.0 years (range, 6.8-28.4) at FAI implantation. Median preoperative best-corrected visual acuity (BCVA) was 0.1 (range, 0.05-0.4) and Standardization of Uveitis Nomenclature, SUN-grade was SUN 2+ (range, 0.5-4.0). All patients had been treated extensively with systemic corticosteroids and antirheumatic drugs by the time of FAI implantation. The median follow-up time was 5.3 years (range, 4.4-6.3).

Results: Macular edema resolved in a median time of 0.2 years (range, 0.04-0.39) after the FAI implantation. The median BCVA was 0.5-0.63 (range, 0.1-1.0) from 1 to 5 years of follow-up. Macular edema did not recur in 5 eyes after the implantation. In three eyes, the macular oedema relapsed at 2.7, 2.9 and 5.5 years of follow-up. All our patients needed antirheumatic drugs in addition to the FAI to treat their macular edema. During the follow-up, 7 eyes required further intraocular operations: 4 cataract operations, 4 intraocular pressure -lowering operations and 1 retinal detachment surgery were performed.

Conclusion: Fluocinolone acetonide implant is a valuable option in the treatment of persistent macular edema associated with JIA-related uveitis refractory to systemic treatments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/aos.13744DOI Listing
September 2018

The Finnish national guideline for diagnosis, treatment and follow-up of patients with wet age-related macular degeneration.

Acta Ophthalmol 2017 07;95(A105 Suppl):1-9

Department of Ophthalmology, Kuopio University Hospital, Kuopio, Finland.

Age-related macular degeneration (AMD) is the main cause of visual impairment in developed countries. Several improvements in the visualization of posterior segment of the eye together with the introduction of intravitreal anti-VEGF treatment have revolutionized the prognosis of the wet form of AMD (wAMD). Increasing incidence of wAMD together with the limited resources of society and of the healthcare system poses challenges for the provision and development of care. In context of these current aspects, we aimed to set evidence-based medical guidelines for diagnosis, treatment and follow-up of patients with wAMD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/aos.13501DOI Listing
July 2017

Protective coding variants in CFH and PELI3 and a variant near CTRB1 are associated with age-related macular degeneration†.

Hum Mol Genet 2016 12;25(23):5276-5285

Ophthalmic Epidemiology and Genetics Service, New England Eye Center, Tufts Medical Center, Boston, MA, USA.

Although numerous common age-related macular degeneration (AMD) alleles have been discovered using genome-wide association studies, substantial disease heritability remains unexplained. We sought to identify additional common and rare variants associated with advanced AMD. A total of 4,332 cases and 25,268 controls of European ancestry from three different populations were genotyped using the Illumina Infinium HumanExome BeadChip. We performed meta-analyses to identify associations with common variants, and single variant and gene-based burden tests to identify rare variants. Two protective, low-frequency, non-synonymous variants were significantly associated with a decrease in AMD risk: A307V in PELI3 (odds ratio [OR] = 0.14, P = 4.3 × 10-10) and N1050Y in CFH (OR = 0.76, P = 6.2 × 10-12). The new variants have a large effect size, similar to some rare mutations we reported previously in a targeted sequencing study, which remain significant in this analysis: CFH R1210C (OR = 18.82, P = 3.5 × 10-07), C3 K155Q (OR = 3.27, P = 1.5 × 10-10) and C9 P167S (OR = 2.04, P = 2.8 × 10-07). We also identified a strong protective signal for a common variant (rs8056814) near CTRB1 associated with a decrease in AMD risk (logistic regression: OR = 0.71, P = 1.8 × 10-07). Suggestive protective loci were identified in the COL4A3 and APOH genes. Our results support the involvement of common and low-frequency protective variants in this vision-threatening condition. This study expands the roles of the innate immune pathway as well as the extracellular matrix and high-density lipoprotein pathways in the aetiology of AMD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/hmg/ddw336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6078639PMC
December 2016

ANTERIOR CHAMBER FLARE DURING BEVACIZUMAB TREATMENT IN EYES WITH EXUDATIVE AGE-RELATED MACULAR DEGENERATION.

Retina 2016 Nov;36(11):2183-2190

*Department of Ophthalmology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; and †School of Management, University of Tampere, Tampere, Finland.

Purpose: To study the anterior chamber flare during bevacizumab treatment of exudative age-related macular degeneration.

Methods: During a 2-year prospective follow-up, 50 patients recently diagnosed with exudative age-related macular degeneration were treated at once-a-month visits if subretinal or intraretinal fluid or a new hemorrhage was present in the lesion area. Flare was measured weekly during the first month and then monthly in both eyes.

Results: Higher flare was associated with older age (P = 0.007, Linear Mixed Model), higher number of smoking pack-years (P = 0.019), macular cysts (P = 0.041), and pseudophakia (P = 0.003). The levels gradually increased during the follow-up (P < 0.0001) but less in the eyes with classic CNV (P = 0.011). Flare decreased during treatment-free periods lasting for at least two consecutive visits (P = 0.005). A peak in flare was observed 1 week after the first injection (P = 0.034, Wilcoxon signed rank test). In the fellow eyes, higher flare values in the beginning of the follow-up were associated with later conversion into exudative age-related macular degeneration (P = 0.015, Mann-Whitney U test).

Conclusion: Anterior chamber flare correlated poorly with the CNV activity. Higher levels may, however, precede or exist early in the process that leads to the development of exudative age-related macular degeneration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/IAE.0000000000001061DOI Listing
November 2016

The genetic variant rs4073 A→T of the Interleukin-8 promoter region is associated with the earlier onset of exudative age-related macular degeneration.

Acta Ophthalmol 2015 Dec 8;93(8):726-33. Epub 2015 Jul 8.

Department of Ophthalmology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Purpose: To study the association of the single nucleotide polymorphism (SNP) rs4073 in the interleukin-8 (IL-8) promoter region with the diagnosis and age of onset of exudative age-related macular degeneration (AMD) in association with the known genetic risk factors for AMD and tobacco smoking.

Methods: Medical records, smoking history and angiograms or fundus photographs of 301 patients with exudative AMD, 72 patients with dry AMD and 119 control subjects were analysed retrospectively. The associations of IL-8 rs4073 A→T, CFH rs1061170 T→C, ARMS2 rs10490924 G→T and C3 rs2230199 C→G SNPs with the presence of AMD and with the age of onset of exudative AMD were analysed.

Results: Younger age of exudative AMD onset was associated with the homozygous AA genotype of IL-8 rs4073 (p = 0.009, Mann-Whitney U-test), CC genotype of CFH rs1061170 (p = 0.016), TT genotype of ARMS2 rs10490924 (p = 0.001) and with current smoking (p = 0.002). The risk alleles C in CFH rs1061170 (p < 0.0001, Pearson chi-square) and T in ARMS2 rs10490924 (p < 0.0001), as well as smoking (p < 0.0001), were more prevalent in AMD patients compared with controls. No association was found between the IL-8 rs4073 genotype and the presence of AMD.

Conclusion: Out of the factors associated with the earlier onset of exudative AMD, only the genotype of IL-8 rs4073 did not appear as a risk factor for AMD in general. IL-8 may have a role in accelerating the development of the choroidal neovascularization in exudative AMD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/aos.12799DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4758390PMC
December 2015

The Schlemm's canal is a VEGF-C/VEGFR-3-responsive lymphatic-like vessel.

J Clin Invest 2014 Sep 25;124(9):3975-86. Epub 2014 Jul 25.

In glaucoma, aqueous outflow into the Schlemm's canal (SC) is obstructed. Despite striking structural and functional similarities with the lymphatic vascular system, it is unknown whether the SC is a blood or lymphatic vessel. Here, we demonstrated the expression of lymphatic endothelial cell markers by the SC in murine and zebrafish models as well as in human eye tissue. The initial stages of SC development involved induction of the transcription factor PROX1 and the lymphangiogenic receptor tyrosine kinase VEGFR-3 in venous endothelial cells in postnatal mice. Using gene deletion and function-blocking antibodies in mice, we determined that the lymphangiogenic growth factor VEGF-C and its receptor, VEGFR-3, are essential for SC development. Delivery of VEGF-C into the adult eye resulted in sprouting, proliferation, and growth of SC endothelial cells, whereas VEGF-A obliterated the aqueous outflow system. Furthermore, a single injection of recombinant VEGF-C induced SC growth and was associated with trend toward a sustained decrease in intraocular pressure in adult mice. These results reveal the evolutionary conservation of the lymphatic-like phenotype of the SC, implicate VEGF-C and VEGFR-3 as critical regulators of SC lymphangiogenesis, and provide a basis for further studies on therapeutic manipulation of the SC with VEGF-C in glaucoma treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1172/JCI75395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4153703PMC
September 2014

The IL-8, VEGF, and CFH polymorphisms and bevacizumab in age-related macular degeneration.

Ophthalmology 2014 Apr 15;121(4):973-973.e1. Epub 2014 Feb 15.

Department of Ophthalmology, Helsinki University Central Hospital, Finland.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ophtha.2013.11.035DOI Listing
April 2014

ADAMTS9 locus associates with increased risk of wet AMD.

Acta Ophthalmol 2014 Aug 16;92(5):e410. Epub 2014 Jan 16.

Institute of Clinical Medicine-Neurology, University of Eastern Finland, Kuopio, Finland ; Department of Neurology, Kuopio University Hospital, Kuopio, Finland.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/aos.12341DOI Listing
August 2014

Increased intravitreal angiopoietin-2 levels associated with rhegmatogenous retinal detachment.

Graefes Arch Clin Exp Ophthalmol 2014 Jun 12;252(6):881-8. Epub 2013 Nov 12.

Unit of Vitreoretinal Surgery, Department of Ophthalmology, Helsinki University Central Hospital, Haartmaninkatu 4 C, 00290, Helsinki, Finland,

Purpose: To explore factors related to pathogenesis of rhegmatogenous retinal detachment (RRD) and development of proliferative vitreoretinopathy (PVR), vitreous levels of angiopoietin-1 and -2 (Ang-1 and -2), previously undefined in RRD, transforming growth factor-(TGF) β1, vascular endothelial growth factor (VEGF), erythropoietin (EPO) and proteolytic mediators of extracellular matrix remodelling (MMP-2 and -9) were compared in eyes with RRD and eyes with idiopathic macular hole or pucker.

Methods: Vitreous samples were collected from 117 eyes with RRD (study group) and 40 eyes with macular hole or pucker (control group). Growth factors were measured by ELISA and matrix metalloproteinases (MMPs) by gelatin zymography.

Results: The mean vitreous concentrations of Ang-2, MMP-2, and MMP-9 were higher (all p < 0.01), whereas concentration of VEGF was lower (p = 0.01) in eyes with RRD relative to controls. Logistic regression analysis identified Ang-2 concentration as a novel marker of RRD (p = 0.0001, OR 48.7). Ang-1, EPO, and total TGF-β1 levels were not significantly different between the groups. However, TGF-β1 and MMP-2 were increased in eyes with total RRD compared to those with local RRD (p ≤ 0.05). In eyes with PVR, no differences were observed in any studied marker as compared with non-PVR eyes.

Conclusions: Current results reveal Ang-2 as a key factor upregulated in RRD. It may co-operate with fibrosis-associated factors and contribute to vascular complications such as breakdown of blood-eye barrier and PVR development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00417-013-2508-zDOI Listing
June 2014

Interleukin 8 promoter polymorphism predicts the initial response to bevacizumab treatment for exudative age-related macular degeneration.

Retina 2013 Oct;33(9):1815-27

*Department of Ophthalmology, Helsinki University Central Hospital, Helsinki, Finland †Department of Medical Genetics, University of Helsinki, Helsinki, Finland Departments of ‡Ophthalmology, Institute of Clinical Medicine, and §Internal Medicine, Clinical Research Center and Biocenter Oulu, University of Oulu, Oulu, Finland ¶Department of Clinical Chemistry, Oulu University Hospital, Oulu, Finland **Department of Biosciences, University of Helsinki, Helsinki, Finland.

Purpose: To study the association of single-nucleotide polymorphisms of interleukin 8, vascular endothelial growth factor, erythropoietin, complement factor H, complement component C3, and LOC387715 genes with the response to bevacizumab treatment in exudative age-related macular degeneration.

Methods: Clinical records, smoking history, optical coherence tomography, and angiographies of 96 bevacizumab-treated exudative age-related macular degeneration patients were analyzed retrospectively. Blood DNA was collected. Based on the disappearance of intra- or subretinal fluid in optical coherence tomography, patients were graded as responders, partial responders, or nonresponders after 3 initial treatment visits and a median time of 3.5 months.

Results: Interleukin 8 promoter polymorphism -251A/T was significantly associated with persisting fluid in optical coherence tomography. The A allele was more frequent in nonresponders than in responders (P = 0.033). In multivariate modeling, the AA genotype of -251A/T (P = 0.043) and occult (P = 0.042) or predominantly classic (P = 0.040) lesions predicted poorer outcome. Visual acuity change was better in responders than in nonresponders (P = 0.006). Baseline lesion size (P = 0.006) and retinal cysts after the treatment (P < 0.001) correlated with less visual acuity gain.

Conclusion: The A allele and the homozygous AA genotype of interleukin 8 -251A/T were associated with anatomical nonresponse to bevacizumab treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/IAE.0b013e318285cf92DOI Listing
October 2013

Ang-2 upregulation correlates with increased levels of MMP-9, VEGF, EPO and TGFβ1 in diabetic eyes undergoing vitrectomy.

Acta Ophthalmol 2013 Sep 26;91(6):531-9. Epub 2012 Oct 26.

Unit of Vitreoretinal Surgery, Department of Ophthalmology, Helsinki University Central Hospital, Finland.

Purpose: Angiogenesis in diabetic retinopathy (DR) is a multifactorial process regulated by hypoxia-induced growth factors and inflammatory cytokines. In addition to the angiogenic switch, the proteolytic processing and altered synthesis of the extracellular matrix are critical steps in this disease. This study was performed to evaluate the levels of matrix metalloproteinase-2 and matrix metalloproteinase-9 (MMP-2 and MMP-9), angiopoietin-1 and angiopoietin-2 (Ang-1 and Ang-2), vascular endothelial growth factor (VEGF), erythropoietin (EPO) and transforming growth factor-β1 (totalTGFβ1) in the vitreous of diabetic eyes undergoing vitrectomy compared with control eyes operated because of macular hole or pucker.

Methods: Prospective consecutive controlled observational study performed in the unit of vitreoretinal surgery in Finland during the years 2006-2008. Vitreous samples were collected before the start of the conventional 3-ppp vitrectomy. Vitreous MMP-2 and MMP-9, Ang-1 and Ang-2, VEGF, EPO and TGFβ1 concentrations were measured from 69 patients with Type 1 or 2 diabetes and 40 controls.

Results: Comparison of eyes with DR with controls revealed that the mean vitreous concentrations of proMMP-2 (p = 0.0015), totalMMP-2 (p = 0.0011), proMMP-9 (p = 0.00001), totalMMP-9 (p < 0.00001), Ang-2 (p < 0.00001), VEGF (p < 0.00001), EPO (p < 0.00001) and totalTGFβ1 (p = 0.000026) were significantly higher in the former group. A multivariate logistic regression analysis suggested intravitreal Ang-2 concentration being the key marker of PDR (p = 0.00025) (OR = 1507.9).

Conclusion: The main new finding is that the intravitreal concentrations of Ang-2 correlated significantly with MMP-9, VEGF, EPO and TGFβ1 levels in diabetic eyes undergoing vitrectomy. Thus, these factors could promote retinal angiogenesis synergistically.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1755-3768.2012.02473.xDOI Listing
September 2013

Correlation between components of newly diagnosed exudative age-related macular degeneration lesion and focal retinal sensitivity.

Acta Ophthalmol 2014 Feb 23;92(1):51-8. Epub 2012 Sep 23.

Department of Ophthalmology, Helsinki University Central Hospital, FinlandDepartment of Biological and Environmental Sciences, University of Helsinki, Finland.

Purpose: To analyse lesion components determining retinal sensitivity in microperimetry in eyes with newly diagnosed exudative age-related macular degeneration (AMD).

Methods: Visual acuity, contrast sensitivity, microperimetry, optical coherence tomography (OCT), and fluorescein (FA) and indocyanine green (ICGA) angiographies of 23 eyes of 23 patients were analysed. Central microperimetry grids with 28 test stimulus sites were automatically aligned with three-dimensional OCTs and manually aligned with angiographies. Thicknesses of the neuroretina, neuroepithelial detachment (NED), retinal pigment epithelial (RPE) elevation and subretinal tissue were measured under the 644 microperimetry stimulus sites. Areas of classic and occult choroidal neovascularizations (CNVs), subretinal and intraretinal haemorrhage, and late hyperfluorescence in ICGA were identified. The impact of the lesion components on retinal sensitivity was evaluated with correlation analysis and multivariate modelling.

Results: Decreased retinal sensitivity correlated significantly with the presence of CNV, haemorrhage, subretinal tissue and RPE elevation. Out of the OCT parameters, the most important determinant of sensitivity was the thickness of RPE elevation (Spearman's rho, r = -0.202, p < 0.0001). The thicknesses of subretinal tissue (r = -0.168, p < 0.0001) and NED had weaker effects (r = -0.147, p < 0.0001), and the neuroretinal thickness remained nonsignificant. In multivariate modelling, RPE elevation and subretinal tissue in OCT, CNV membranes in angiographies and haemorrhage had the strongest impacts on retinal sensitivity.

Conclusion: The most important lesion components affecting retinal function were RPE elevation and subretinal tissue in OCT as well as neovascular membranes and haemorrhage in angiographies. NED and neuroretinal thickening remained less significant.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1755-3768.2012.02556.xDOI Listing
February 2014

Leucocyte telomere length in age-related macular degeneration.

Acta Ophthalmol 2013 Aug 2;91(5):453-6. Epub 2012 May 2.

Department of Ophthalmology, Helsinki University Hospital, Helsinki, Finland.

Purpose: To evaluate the association between telomere length and age-related macular degeneration (AMD).

Methods: Circulating leucocyte telomere length and the proportion of telomeres <5 kb were analysed in blood DNA samples taken from 121 patients with exudative AMD (83%), large drusen (14%) or central geographic atrophy (3%). Controls consisted of 77 age-matched subjects without AMD. The AMD status was assessed by a masked analysis of fundus photographs or angiographs. Telomere length was measured by Southern blotting.

Results: Mean (SD) telomere length was 7.76 kb (0.68) in AMD patients and 7.83 (0.69) in controls (p = 0.485). The corresponding proportions of telomeres <5 kb were 10.60 (2.76) and 10.05 (2.64) (p = 0.197). In this material, there was no correlation between telomere length and age, gender or smoking status. There were no differences between the major AMD risk single-nucleotide polymorphisms (SNPs) of the CFH, HTRA1 or C3 genes, expect for somewhat longer telomeres in controls with the C3 risk SNP. There were no differences in telomere length between patients with drusen or exudative AMD.

Conclusions: Telomere length is not associated with exudative AMD or high-risk drusen.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1755-3768.2012.02427.xDOI Listing
August 2013

Adiponectin receptor 1 gene (ADIPOR1) variant is associated with advanced age-related macular degeneration in Finnish population.

Neurosci Lett 2012 Apr 25;513(2):233-7. Epub 2012 Feb 25.

Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland; Department of Ophthalmology, Kuopio University Hospital, Kuopio, Finland.

Adiponectin is an adipocyte-expressed protein that regulates the glucose, lipid, and energy metabolism via adiponectin receptors 1 and 2. Obesity is a known risk factor for age-related macular degeneration (AMD). We, therefore, examined associations of single nucleotide polymorphisms in Adiponectin (ADIPOQ) and Adiponectin receptors 1 and 2 (ADIPOR1 and ADIPOR2) genes with the prevalence of advanced AMD in Finnish population. Thirty-seven markers for ADIPOQ, ADIPOR1 and ADIPOR2 were genotyped in a sample collection of 91 men and 177 women having exudative AMD and 18 men and 26 women having severe atrophic AMD. Patients were diagnosed by fundus photographs and fluorescein angiography. The control group (no signs of AMD in fundus photographs) consisted of 55 men and 111 women. Inclusion criteria age was over 65 years old without diabetes diagnosis. Out of the tested SNPs, rs10753929 located in intron of ADIPOR1 gene was significantly associated (p=0.0471) with AMD status when using a permutation procedure that controlled for the number of tested genotypes and genetic models. Odds ratio (OR) for the association was 1.699 (95% CI 1.192-2.423). The SNP consists of C/T alleles and the risk allele T had a minor allele frequency (MAF) of 20.4%. Distribution of proportion of cases/controls between alleles revealed an additive genetic model. Our findings reveal that rs10753929 ADIPOR1 variant is a novel candidate for AMD genetic risk factor in Finnish population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neulet.2012.02.050DOI Listing
April 2012

Photodynamic ablation of lymphatic vessels and intralymphatic cancer cells prevents metastasis.

Sci Transl Med 2011 Feb;3(69):69ra11

Molecular/Cancer Biology Laboratory, Faculty of Medicine Research Programs, Haartman Institute, Institute for Molecular Medicine Finland and Helsinki University Central Hospital, Biomedicum Helsinki, POB 63 (Haartmaninkatu 8), University of Helsinki, 00014 Helsinki, Finland.

The dissemination of tumor cells to sites far from the primary tumor (metastasis) is the principal cause of death in cancer patients. Tumor-associated lymphatic vessels are a key conduit for metastatic tumor cells, which typically first colonize the lymph nodes. Although the primary tumor and affected lymph nodes can be removed during surgery, tumor cells inside lymphatic vessels are left behind. Here, we show that in-transit tumor cells inside lymphatic vessels in mice bearing mouse melanomas or human lung tumors give rise to metastases. Using photodynamic therapy with the benzoporphyrin derivative verteporfin, we selectively destroyed lymphatic vessels in mice and pigs. Destruction of tumor-associated lymphatic vessels also eradicated intralymphatic tumor cells and prevented metastasis of mouse melanoma cells and subsequent relapse. Photodynamic therapy, when combined with anti-lymphangiogenic therapy, prevented further tumor invasion of lymphatic vessels. These findings highlight the potential of targeting in-transit tumor cells in patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/scitranslmed.3001699DOI Listing
February 2011

Screening of DNA-variants in the properdin gene (CFP) in age-related macular degeneration (AMD).

Mol Immunol 2010 Mar 31;47(6):1334-6. Epub 2010 Jan 31.

Department of Ophthalmology, University of Helsinki, Helsinki, Finland.

Several variants in the complement cascade genes (complement factor H [CFH], C2, C3, CFB, and Serping1) have been reported to associate with age-related macular degeneration (AMD). Of these, a member of the complement alternative pathway, CFH, represents the highest risk. As properdin (P) is also an important protein in this pathway, we analysed whether variants in the properdin gene (CFP) at Xp11.4 are associated with AMD. Ten exons of CFP were sequenced in a total of 222 Finnish patients with AMD (150 sporadic cases and 72 familial cases). The controls were 86 age-matched non-AMD patients with no large drusen and no or minimal focal pigmentary abnormalities. A total of four single nucleotide polymorphisms (SNPs) were detected in CFP, three of them infrequent (in 5 patients and controls in total). The fourth SNP, rs1048118 in exon 10, was more frequent, but was not associated with AMD, either alone (p=0.33) or in conjunction with other risk factors. Thus, CFP does not seem to confer any risk for AMD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.molimm.2010.01.001DOI Listing
March 2010

[Identification of susceptibility genes for age-related macular degeneration--a success story of molecular genetics].

Duodecim 2009 ;125(21):2360-4

HUS:n silmäsairaala, Haartmaninkatu 2, 00290 Helsinki, ja Helsingin yliopisto, Biomedicum, lääketieteellisen, genetiikan osasto.

The number of persons over 70 years of age with advanced age-related macular degeneration in Finland can be estimated to be approximately 50,000. Milder forms are additionally present in a considerably larger group. Smoking and age are undisputed non-genetic risk factors of age-related macular degeneration. Of the genetic factors, polymorphisms of the complement factor H (CFH) and LOC387715 genes have a strong impact on the risk of developing the disease, whereas alleles of the C3, CFB, and the C1 inhibitor SERPING1 genes of the complement system exhibit only minor effects.
View Article and Find Full Text PDF

Download full-text PDF

Source
January 2010

Vascular endothelial growth factor gene variation and the response to photodynamic therapy in age-related macular degeneration.

Ophthalmology 2010 Jan 6;117(1):103-8. Epub 2009 Nov 6.

Department of Ophthalmology, Helsinki University Hospital, Helsinki, Finland.

Purpose: To evaluate the role of vascular endothelial growth factor (VEGF) gene polymorphisms in exudative age-related macular degeneration (AMD).

Design: Retrospective, comparative case series.

Participants: Patients with recent exudative AMD (n = 162) and age-matched subjects without AMD (n = 85).

Methods: Fluorescein angiography (FA), clinical examination, and single nucleotide polymorphism (SNP) genotyping.

Main Outcome Measures: The frequencies of 3 VEGF gene SNPs were analyzed, 1 at the promoter site (rs699947, A-->C) and 2 intronic SNPs (rs2146323, A-->C, and rs3025033, A-->G), in relation to the risk of AMD, to choroidal neovascular (CNV) lesion size and configuration, and to the anatomic response to photodynamic therapy (PDT). These SNPs were chosen to cover all the haploblocks of the VEGF gene. The 86 patients who had undergone PDT were classified as either PDT responders or PDT nonresponders based on the outcome of PDT after the last treatment session. For the PDT responders, the treating physician had deemed the lesion to be clinically dry and without leakage from CNV in FA at a visit scheduled at least 12 weeks after the last PDT treatment. For the PDT nonresponders, the PDT sessions had been discontinued by the treating retina specialist because of an apparently poor response and a still exudative lesion after several PDT sessions.

Results: The presence of exudative AMD or lesion size or configuration was not associated with the SNPs studied here. The frequencies of the rs699947 were significantly different in PDT nonresponders and PDT responders. The AA, AC, and CC genotypes were 14%, 39%, and 46%, respectively, in PDT nonresponders, compared with 40%, 48%, and 12%, respectively, in the PDT responders (P = 0.0008). The corresponding frequencies for the rs2146323 AA, AC, and CC genotypes were 4%, 32%, and 64%, respectively, in nonresponders and 24%, 38%, and 38%, respectively, in responders (P = 0.0369). The genotypes of the rs3025033 SNP were distributed evenly between the responders and nonresponders.

Conclusions: The VEGF gene polymorphic SNPs at rs699947 and rs2146323 are strong determinants of the anatomic outcome after PDT, but the SNPs studied were not associated with the presence of exudative AMD or with the CNV lesion size or configuration.

Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ophtha.2009.06.037DOI Listing
January 2010

Single nucleotide polymorphisms of the tenomodulin gene (TNMD) in age-related macular degeneration.

Mol Vis 2009 15;15:762-70. Epub 2009 Apr 15.

Department of Clinical Nutrition and Food and Health Research Centre, University of Kuopio, Kuopio, Finland.

Purpose: Tenomodulin (TNMD) is located in the X-chromosome encoding a putative angiogenesis inhibitor which is expressed in retina. Associations of single nucleotide polymorphisms of TNMD with the prevalence of age-related macular degeneration (AMD) were examined.

Methods: Six markers covering 75% of the common sequence variation in the coding region of TNMD and 10 kb up- and downstream were genotyped in a sample consisting of 89 men and 175 women with exudative AMD, 18 men and 25 women with atrophic AMD, and 55 men and 113 women without AMD. All participants were over 65 years old and did not have diabetes mellitus. Due to the chromosomal locus, the association of genotypes with AMD was assessed genderwise.

Results: Three markers, rs1155974, rs2073163, and rs7890586, were associated with a risk of AMD in women. In comparison to women with other genotypes, the women who were homozygous for the minor allele (genotypes rs1155974-TT or rs2073163-CC) had 2.6 fold (p=0.021) or 1.9 fold (p=0.067) risk for having AMD, respectively. These differences were due to the unequal prevalence of exudative AMD. In comparison to women who were homozygous for the major alleles, the women with rs1155974-TT genotype had a 2.8 fold risk (p=0.021 in additive model; p=0.022 in recessive model) for exudative AMD, and the women with rs2073163-CC genotype had a 1.8 fold risk (p=0.09 in additive model; p=0.038 in recessive model). Furthermore, women carrying the rare rs7890586-AA genotype had a significantly smaller risk for having AMD than women with the other genotypes (odds ratio 0.083; p=0.001 in recessive model), but due to the low frequency of this genotype, this finding must be interpreted cautiously. The false discovery rate was <10% for all of the aforementioned results.

Conclusions: On the basis of the putative antiangiogenic role of TNMD and the present genetic associations of TNMD with AMD in women, we suggest that TNMD could be a novel candidate gene for AMD. These results should be confirmed in further studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2669446PMC
May 2009

[Pathogenesis of age-related macular degeneration].

Duodecim 2009 ;125(2):145-53

Kuopion yliopisto ja KYS:n silmätautien yksikkö.

Age-related macular degeneration is a multiform disease of the macula, the region responsible for detailed central vision. In recent years, plenty of new knowledge of the pathogenesis of this disease has been obtained, and the treatment of exudative macular degeneration has greatly progressed. The number of patients with age-related macular degeneration will multiply in the following decades, because knowledge of mechanisms of development of macular degeneration that could be subject to therapeutic measures is insufficient. Central underlying factors are genetic inheritance, exposure of the retina to chronic oxidative stress and accumulation of inflammation-inducing harmful proteins into or outside of retinal cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
May 2009

Macular blood flow measured by blue-field entoptoscopy and Heidelberg retinal flowmetry: comparison of two techniques in type 1 diabetes women during pregnancy.

Acta Ophthalmol 2009 Aug 3;87(5):506-10. Epub 2008 Dec 3.

Department of Ophthalmology, Helsinki University Central Hospital, Finland.

Purpose: This study compared macular capillary leucocyte velocity values measured with a psychophysical blue-field entoptic simulation (BFS) technique and confocal scanning laser Doppler flowmetry.

Methods: A cross-sectional study was performed where macular capillary leucocyte velocity was measured by BFS using an Oculix BFS-2000 V2.1 psychophysical system and by confocal scanning laser Doppler flowmetry using Heidelberg retinal flowmetry (HRF) in 35 type 1 diabetes women during the second trimester.

Results: The macular leucocyte velocities measured with BFS correlated significantly with the 50th percentile (r = 0.345, p = 0.042, n = 35, Spearman's non-parametric correlation), the 75th percentile (r = 0.432, p = 0.009) and the 90th percentile (r = 0.373, p = 0.027) of HRF flow values during the second trimester. However, there was no correlation between BFS velocity and the 25th percentile of HRF measurements.

Conclusions: Blue-field simulation is known to be an experimental technique that provides a quantitative measure of flow in the perifoveal capillary network. By contrast, HRF imaging reflects quantitative, multispectral, objective and non-invasive measurements in a two-dimensional projection of a three-dimensional retinal capillary bed. Our study showed that BFS velocity was correlated with HRF values in a group of women with diabetes during pregnancy. The positive correlation between BFS and HRF values suggests that the psychophysical BFS and scanning laser-based HRF measure similar functions in the retina.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1755-3768.2008.01303.xDOI Listing
August 2009

Multifactor effects and evidence of potential interaction between complement factor H Y402H and LOC387715 A69S in age-related macular degeneration.

PLoS One 2008 2;3(12):e3833. Epub 2008 Dec 2.

Department of Ophthalmology, University of Helsinki, Helsinki, Finland.

Background: Variants in the complement cascade genes and the LOC387715/HTRA1, have been widely reported to associate with age-related macular degeneration (AMD), the most common cause of visual impairment in industrialized countries.

Methods/principal Findings: We investigated the association between the LOC387715 A69S and complement component C3 R102G risk alleles in the Finnish case-control material and found a significant association with both variants (OR 2.98, p = 3.75 x 10(-9); non-AMD controls and OR 2.79, p = 2.78 x 10(-19), blood donor controls and OR 1.83, p = 0.008; non-AMD controls and OR 1.39, p = 0.039; blood donor controls), respectively. Previously, we have shown a strong association between complement factor H (CFH) Y402H and AMD in the Finnish population. A carrier of at least one risk allele in each of the three susceptibility loci (LOC387715, C3, CFH) had an 18-fold risk of AMD when compared to a non-carrier homozygote in all three loci. A tentative gene-gene interaction between the two major AMD-associated loci, LOC387715 and CFH, was found in this study using a multiplicative (logistic regression) model, a synergy index (departure-from-additivity model) and the mutual information method (MI), suggesting that a common causative pathway may exist for these genes. Smoking (ever vs. never) exerted an extra risk for AMD, but somewhat surprisingly, only in connection with other factors such as sex and the C3 genotype. Population attributable risks (PAR) for the CFH, LOC387715 and C3 variants were 58.2%, 51.4% and 5.8%, respectively, the summary PAR for the three variants being 65.4%.

Conclusions/significance: Evidence for gene-gene interaction between two major AMD associated loci CFH and LOC387715 was obtained using three methods, logistic regression, a synergy index and the mutual information (MI) index.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0003833PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2585793PMC
January 2009

Crosstalk between Hsp70 molecular chaperone, lysosomes and proteasomes in autophagy-mediated proteolysis in human retinal pigment epithelial cells.

J Cell Mol Med 2009 Sep 6;13(9B):3616-31. Epub 2008 Nov 6.

Department of Ophthalmology, University of Kuopio, Kuopio, Finland.

The pathogenesis of age-related macular degeneration involves chronic oxidative stress, impaired degradation of membranous discs shed from photoreceptor outer segments and accumulation of lysosomal lipofuscin in retinal pigment epithelial (RPE) cells. It has been estimated that a major part of cellular proteolysis occurs in proteasomes, but the importance of proteasomes and the other proteolytic pathways including autophagy in RPE cells is poorly understood. Prior to proteolysis, heat shock proteins (Hsps), agents that function as molecular chaperones, attempt to refold misfolded proteins and thus prevent the accumulation of cytoplasmic protein aggregates. In the present study, the roles of the Hsp70 molecular chaperone and proteasomal and lysosomal proteolytic pathways were evaluated in human RPE cells (ARPE-19). The Hsp70 and ubiquitin protein levels and localization were analysed by Western blotting and immunofluorescense. Confocal and transmission electron microscopy were used to detect cellular organelles and to evaluate the morphological changes. Hsp70 levels were modulated using RNA interference and overexpression techniques. Cell viability was measured by colorimetric assay. The proteasome inhibitor MG-132 evoked the accumulation of perinuclear aggregates positive for Hsp70, ubiquitin-protein conjugates and the lysosomal membrane protein LAMP-2. Interestingly, the hsp70 mRNA depletion significantly increased cell death in conjunction with proteasome inhibition. We found that the accumulation of lysosomes was reversible: a cessation of proteasome inhibition led to clearance of the deposits via a mechanism believed to include autophagy. The molecular chaperone Hsp70, proteasomes and autophagy have an important regulatory role in the protein turnover of human RPE cells and may thus open new avenues for understanding degenerative processes in retinal cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1582-4934.2008.00577.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4516511PMC
September 2009

Cyclophotocoagulation with the transscleral contact red 670-nm diode laser in the treatment of glaucoma.

Acta Ophthalmol 2008 Aug;86(5):558-64

Helsinki University Eye Hospital, Helsinki, Finland.

Purpose: To retrospectively evaluate the results of cyclophotocoagulation (CPC) with the transscleral contact red 670-nm diode laser in treating glaucoma.

Methods: Cyclophotocoagulation was performed in 60 eyes of 60 patients with a mean age of 74 +/- 11 years (range 49-90 years). The treatment was delivered via a fibre-optic probe. The power per application was 430 mW. Exposure time was 10 seconds.

Results: The mean overall follow-up time after the initial CPC was 26 +/- 20 months (range 3-75 months). Preoperative intraocular pressure (IOP) was 27 +/- 11 mmHg (n = 60). After one or more CPC treatments, mean IOP decreased to 20 +/- 7 mmHg (n = 51) at 1 month, 19 +/- 5 mmHg (n = 45) at 3 months, 18 +/- 5 mmHg (n = 29) at 6 months, 19 +/- 7 mmHg (n = 22) at 1 year, 18 +/- 7 mmHg (n = 16) at 2 years, 14 +/- 4 mmHg (n = 8) at 3 years, and 18 +/- 6 mmHg (n = 60) at the last follow-up. An IOP of 8-21 mmHg or a > 30% decrease in IOP was obtained in 33 of 41 eyes (80%) with baseline IOP > 21 mmHg at the last follow-up. Hypotonia (IOP < 8 mmHg) did not develop in any of the eyes studied.

Conclusions: Cyclophotocoagulation with the red 670-nm diode laser is an effective and well tolerated means of treating glaucoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1600-0420.2007.01090.xDOI Listing
August 2008

Complement factor H Y402H polymorphism and characteristics of exudative age-related macular degeneration lesions.

Acta Ophthalmol 2008 Jun 7;86(4):390-4. Epub 2007 Nov 7.

Department of Ophthalmology, Helsinki University Central Hospital, Helsinki, Finland.

Purpose: The Y402H polymorphism of the complement factor H (CFH) gene is associated with age-related macular degeneration (AMD) in many populations. The reported genotype-phenotype correlations in the CFH Y402H polymorphism have not been pronounced and no studies on the effect of the polymorphism on the subgroups within wet AMD have been performed. In this study, we wanted to evaluate whether the CFH Y402H polymorphism has an effect on clinical variables in recent exudative AMD lesions.

Methods: The study included 172 patients with exudative AMD. The size of AMD lesions and the presence and area of other AMD lesion variables were recorded in fluorescein angiography (FA) and analysed in relation to the Y402H genotypes.

Results: The median lesion size (classic + occult choroidal neovascularization [CNV] + serous pigment epithelium detachment [PED] + haemorrhage, if present) was 8.15 mm(2) in patients homozygous for the CFH risk allele (CC), 7.50 mm(2) in heterozygous patients (CT), and 7.05 mm(2) in those with the normal genotype (TT) (p = 0.599). Areas of classic and occult CNV, combined, without serous PED or haemorrhage were 6.37 mm(2), 5.00 mm(2) and 5.18 mm(2), respectively (p = 0.407). There was a trend for CC patients to have more frequently minimally classic and less frequently predominantly classic lesion composition than CT or TT subjects.

Conclusions: We detected no clear impact of the CFH Y402H polymorphism on recent exudative AMD lesion characteristics. Although the complement cascade is implicated in CNV formation and scarring processes in the retina, the Y402H polymorphism appears relatively neutral in these functions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1600-0420.2007.01050.xDOI Listing
June 2008

Y402H polymorphism of complement factor H affects binding affinity to C-reactive protein.

J Immunol 2007 Mar;178(6):3831-6

Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Haartmaninkatu 3, FI-00014 Helsinki, Finland.

Complement factor H (FH) is an important regulator of the alternative complement pathway. The Y402H polymorphism within the seventh short consensus repeat of FH was recently shown to be associated with age-related macular degeneration, the most common cause of irreversible blindness in the Western world. We examined the effects of this polymorphism on various FH functions. FH purified from sera of age-related macular degeneration patients homozygous for the FH(402H) variant showed a significantly reduced binding to C-reactive protein (CRP), an acute phase protein, as compared with FH derived from unaffected controls homozygous for the FH(402Y) variant. Strongly reduced binding to CRP was also observed with a recombinant fragment of FH (short consensus repeat 5-7) containing the same amino acid change. Because the interaction of CRP and FH promotes complement-mediated clearance of cellular debris in a noninflammatory fashion, we propose that the reduced binding of FH(402H) to CRP could lead to an impaired targeting of FH to cellular debris and a reduction in debris clearance and enhanced inflammation along the macular retinal pigmented epithelium-choroid interface in individuals with age-related macular degeneration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4853917PMC
http://dx.doi.org/10.4049/jimmunol.178.6.3831DOI Listing
March 2007

Primary intraocular lymphoma: improving the diagnostic procedure.

Ophthalmology 2007 Jul 26;114(7):1372-7. Epub 2007 Feb 26.

Department of Ophthalmology, University of Helsinki, Helsinki, Finland.

Objective: To analyze the clinical features of primary intraocular lymphoma (PIOL) and to describe cytochemical and immunocytochemical findings of the vitreous specimens as well as the reasons for delayed diagnosis of PIOL.

Design: Prospective noncomparative study.

Participants: Eleven patients referred to the uveitis or medical retina units, Department of Ophthalmology, University of Helsinki, were diagnosed as having PIOL between 2000 and 2005. The median follow-up of the patients was 32 months.

Methods: Clinical features and diagnostic workup of uveitis were described. Twelve vitrectomies were performed on 9 patients. The first 5 biopsies were fixed in an equal volume of 50% alcohol. The specimens of the next 7 vitrectomies were handled without alcohol, and tissue culture medium was added to the samples.

Main Outcome Measures: Clinical features of PIOL, intervals from ocular symptoms and from first ophthalmological examination to diagnosis, and the role of a proper handling of the vitreous sample in the diagnosis of PIOL.

Results: Six females (54%) and 5 males (46%) (median age, 61 years) were included. Ten patients had ocular symptoms for 1 to 30 months (median, 8) before the first contact with an ophthalmologist. Uveitis was bilateral in 9 patients. Vitreitis was seen in all patients, and it was severe in 8. Fundus lesions dominated in 3 patients. Six patients lost useful vision in one eye before the diagnosis of PIOL. Cytologic and immunohistochemical stainings prepared of the unfixed vitreous specimens showed PIOL in 6 patients. The samples fixed in alcohol were nondiagnostic in 4 patients, and in them, verification of diagnosis was based on brain biopsy (3) or cerebrospinal fluid (1) findings. Seven patients died due to primary nervous system lymphoma.

Conclusions: Diagnosis of PIOL is difficult but can be improved. Severe bilateral vitreitis in an elderly patient is a characteristic finding of PIOL. Alcohol fixation may jeopardize the identification of PIOL cells in the vitreous sample. Optimal handling of the vitreous specimens and examination of the slides by an experienced cytopathologist are critical in the diagnostic workup of PIOL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ophtha.2006.11.009DOI Listing
July 2007

Leucine 7-proline 7 polymorphism in the signal peptide of neuropeptide Y is not a risk factor for exudative age-related macular degeneration.

Acta Ophthalmol Scand 2007 Mar;85(2):188-91

Department of Ophthalmology, University of Kuopio, Kuopio, Finland.

Purpose: Because of the regulatory role of neuropeptide Y (NPY) in angiogenesis, we set out to determine the presence of the leucine 7-proline 7 (Leu7Pro) polymorphism in exudative age-related macular degeneration (AMD) patients and to analyse its implications.

Methods: Genotype analysis of the Leu7Pro polymorphism in the signal peptide region of the human prepro-NPY was performed in blood samples from exudative AMD patients (n = 240) and control subjects (n = 79).

Results: In all, 11% of exudative AMD patients and 14% of control subjects exhibited the NPY signal peptide Leu7Pro polymorphism. There were no statistically significant differences in Leu7Pro polymorphism frequency between the exudative AMD and control cases, as analysed by Fisher's exact two-sided test.

Conclusions: Leu7Pro polymorphism in the signal peptide region of the human prepro-NPY is not a risk factor for exudative AMD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1600-0420.2006.00787.xDOI Listing
March 2007