Publications by authors named "Sirpa Loukovaara"

43 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.
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http://dx.doi.org/10.1111/aos.14774DOI Listing
February 2021

Statins for the prevention of proliferative vitreoretinopathy: cellular responses in cultured cells and clinical statin concentrations in the vitreous.

Sci Rep 2021 01 13;11(1):980. Epub 2021 Jan 13.

School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Yliopistonranta 1C, P.O.B. 1627, 70211, Kuopio, Finland.

Proliferative vitreoretinopathy (PVR) with rhegmatogenous retinal detachment (RRD) is a complex inflammatory ocular disease. Statins are widely used cholesterol-lowering drugs with putative anti-inflammatory properties. In this study, we have explored their efficacy in controlling post-surgical PVR formation. Simvastatin (SIM), atorvastatin (ATV), or rosuvastatin (RSV) were added to cultures of human retinal pigment epithelial cells (ARPE-19) prior to exposure with the bacterial lipopolysaccharide (LPS), and the production of pro-inflammatory cytokines (IL-6, IL-8, MCP-1) was examined using an enzyme-linked immunosorbent assay. In addition, the concentrations of simvastatin, atorvastatin, rosuvastatin, and their metabolites were measured from the vitreal samples of 20 patients undergoing vitrectomy (16 of them receiving oral statin therapy) using an ultra-performance liquid chromatography-tandem mass spectrometer technique. All statins alleviated LPS-induced inflammation at 5 µM concentration in the ARPE-19 cell cultures. Statin levels in the vitreous samples ranged from 6 to 316 pg/mL (ca. 0.1-7 M). Vitreal statin concentrations were similar to the typical steady-state unbound statin concentrations in plasma, indicating that only the unbound drug distributes from the blood circulation into the vitreous. Pharmacokinetic simulations of the intravitreal delivery of statins indicate that the measured clinical statin concentrations could be maintained with existing drug delivery technologies for months. Our results suggest that intravitreal statin therapy may have the potential in alleviating the risk of post-surgical PVR.
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http://dx.doi.org/10.1038/s41598-020-80127-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806714PMC
January 2021

Molecular pathogenesis of rhegmatogenous retinal detachment.

Sci Rep 2021 Jan 13;11(1):966. Epub 2021 Jan 13.

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

Rhegmatogenous retinal detachment (RRD) is an ophthalmic emergency, which usually requires prompt surgery to prevent further detachment and restore sensory function. Although several individual factors have been suggested, a systems level understanding of molecular pathomechanisms underlying this severe eye disorder is lacking. To address this gap in knowledge we performed the molecular level systems pathology analysis of the vitreous from 127 patients with RRD using state-of-the art quantitative mass spectrometry to identify the individual key proteins, as well as the biochemical pathways contributing to the development of the disease. RRD patients have specific vitreous proteome profiles compared to other diseases such as macular hole, pucker, or proliferative diabetic retinopathy eyes. Our data indicate that various mechanisms, including glycolysis, photoreceptor death, and Wnt and MAPK signaling, are activated during or after the RRD to promote retinal cell survival. In addition, platelet-mediated wound healing processes, cell adhesion molecules reorganization and apoptotic processes were detected during RRD progression or proliferative vitreoretinopathy formation. These findings improve the understanding of RRD pathogenesis, identify novel targets for treatment of this ophthalmic disease, and possibly affect the prognosis of eyes treated or operated upon due to RRD.
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http://dx.doi.org/10.1038/s41598-020-80005-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806834PMC
January 2021

Intravitreal anti-VEGF therapy is not associated with a higher risk of all-cause mortality in patients with macular oedema caused by posterior segment vascular diseases.

Acta Ophthalmol 2021 Jan 2. Epub 2021 Jan 2.

Department of Public Health, University of Helsinki, Helsinki, Finland.

Purpose: To examine whether real-world clinical patients with macular oedema (MO) receiving intravitreal antivascular endothelial growth factor (VEGF) therapy have a higher mortality compared with a matched reference population.

Methods: A population-based, retrospective cohort study of 26 386 patients from Finland, from January 1, 2001, to December 31, 2017. Index patients were identified through the Caring Epidemiology Project database, receiving at least one intravitreal anti-VEGF injection for wet age-related macular degeneration (AMD, n = 2243, 48.61%), diabetic MO (n = 744, 16.12%), MO due to retinal vascular occlusion (n = 589, 12.77%), or other MO (n = 1038, 22.5%). For each individual treated with intravitreal injection (n = 4614), five age- , sex- , calendar year- and hospital district- matched control individuals (n = 21 772) were chosen. Baseline data of chronic conditions were available. All-cause and cause-specific mortality was analysed using Cox´s proportional hazards model.

Results: In general, the anti-VEGF treated patients had a higher prevalence of systemic conditions, including diabetes (60.1% vs. 46.8%, p < 0.001), chronic hypertension (38.4% vs. 34.6%, p < 0.001), in hospital-treated ischaemic heart disease (23.1% vs. 21.5%, p = 0.014), and glaucoma (11.1% vs. 6.3%, p < 0.001) than controls. There was no difference in all-cause mortality between the anti-VEGF treated patients and matched controls (p = 0.62). In unadjusted Kaplan-Meier analysis of wet AMD subgroup, all-cause mortality was lower in anti-VEGF treated patients than matched controls (p = 0.015), but adjusted Cox´s proportional hazards model showed no difference in the risk of all-cause mortality (HR 0.85, 95% CI 0.66-1.09).

Conclusions: Intravitreal anti-VEGF therapy was not associated with an increase in the risk of mortality in patients with MO compared with age- and sex-matched controls.
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http://dx.doi.org/10.1111/aos.14717DOI Listing
January 2021

Cancer is associated with a 2.7 higher risk for intravitreal injection therapy in patients with age-related, diabetic, or vascular occlusive macular edema.

Acta Ophthalmol 2020 Aug 24. Epub 2020 Aug 24.

Department of Public Health, University of Helsinki, Helsinki, Finland.

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http://dx.doi.org/10.1111/aos.14546DOI Listing
August 2020

Pathogenic causes and outcomes of endophthalmitis after vitreoretinal surgeries in Finland from 2009 to 2018.

Acta Ophthalmol 2020 Feb 28;98(1):e128-e130. Epub 2019 Jul 28.

Inflammation Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

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http://dx.doi.org/10.1111/aos.14187DOI Listing
February 2020

Topical levofloxacin, nepafenac and prednisolone acetate medication after cataract surgery in the biggest tertiary eye hospital in Finland during 2015-2018.

Acta Ophthalmol 2019 Sep 27;97(6):e943-e945. Epub 2019 Mar 27.

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

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http://dx.doi.org/10.1111/aos.14091DOI Listing
September 2019

An Ex Vivo Tissue Culture Model for Fibrovascular Complications in Proliferative Diabetic Retinopathy.

J Vis Exp 2019 01 25(143). Epub 2019 Jan 25.

Research Programs Unit, Genome-Scale Biology, Biomedicum Helsinki, University of Helsinki; Department of Microbiology, Tumor, and Cell Biology (MTC), Karolinska Institutet;

Diabetic retinopathy (DR) is the most common microvascular complication of diabetes and one of the leading causes of blindness in working-age adults. No current animal models of diabetes and oxygen-induced retinopathy develop the full-range progressive changes manifested in human proliferative diabetic retinopathy (PDR). Therefore, understanding of the disease pathogenesis and pathophysiology has relied largely on the use of histological sections and vitreous samples in approaches that only provide steady-state information on the involved pathogenic factors. Increasing evidence indicates that dynamic cell-cell and cell-extracellular matrix (ECM) interactions in the context of three-dimensional (3D) microenvironments are essential for the mechanistic and functional studies towards the development of new treatment strategies. Therefore, we hypothesized that the pathological fibrovascular tissue surgically excised from eyes with PDR could be utilized to reliably unravel the cellular and molecular mechanisms of this devastating disease and to test the potential for novel clinical interventions. Towards this end, we developed a novel method for 3D ex vivo culture of surgically-excised patient-derived fibrovascular tissue (FT), which will serve as a relevant model of human PDR pathophysiology. The FTs are dissected into explants and embedded in fibrin matrix for ex vivo culture and 3D characterization. Whole-mount immunofluorescence of the native FTs and end-point cultures allows thorough investigation of tissue composition and multicellular processes, highlighting the importance of 3D tissue-level characterization for uncovering relevant features of PDR pathophysiology. This model will allow the simultaneous assessment of molecular mechanisms, cellular/tissue processes and treatment responses in the complex context of dynamic biochemical and physical interactions within the PDR tissue architecture and microenvironment. Since this model recapitulates PDR pathophysiology, it will also be amenable for testing or developing new treatments.
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http://dx.doi.org/10.3791/59090DOI Listing
January 2019

Soluble and membrane-bound adenylate kinase and nucleotidases augment ATP-mediated inflammation in diabetic retinopathy eyes with vitreous hemorrhage.

J Mol Med (Berl) 2019 03 7;97(3):341-354. Epub 2019 Jan 7.

MediCity Research Laboratory, University of Turku, Tykistökatu 6A, 20520, Turku, Finland.

ATP and adenosine are important signaling molecules involved in vascular remodeling, retinal function, and neurovascular coupling in the eye. Current knowledge on enzymatic pathways governing the duration and magnitude of ocular purinergic signaling is incompletely understood. By employing sensitive analytical assays, this study dissected ocular purine homeostasis as a complex and coordinated network. Along with previously characterized ecto-5'-nucleotidase/CD73 and adenylate kinase activities, other enzymes have been identified in vitreous fluids, including nucleoside triphosphate diphosphohydrolase (NTPDase), adenosine deaminase, and alkaline phosphatase. Strikingly, activities of soluble adenylate kinase, adenosine deaminase, ecto-5'-nucleotidase/CD73, and alkaline phosphatase, as well as intravitreal concentrations of ATP and ADP, were concurrently upregulated in patients suffering from diabetic retinopathy (DR) with non-clearing vitreous hemorrhage (VH), when compared to DR eyes without VH and control eyes operated due to macular hole or pucker. Additional histochemical analysis revealed selective distribution of key ecto-nucleotidases (NTPDase1/CD39, NTPDase2, ecto-5'-nucleotidase/CD73, and alkaline phosphatase) in the human sensory neuroretina and optic nerve head, and also in pathological neofibrovascular tissues surgically excised from patients with advanced proliferative DR. Collectively, these data provide evidence for specific hemorrhage-related shifts in purine homeostasis in DR eyes from the generation of anti-inflammatory adenosine towards a pro-inflammatory and pro-angiogenic ATP-regenerating phenotype. In the future, identifying the exact mechanisms by which a broad spectrum of soluble and membrane-bound enzymes coordinately regulates ocular purine levels and the further translation of purine-converting enzymes as potential therapeutic targets in the treatment of proliferative DR and other vitreoretinal diseases will be an area of intense interest. KEY MESSAGES: NTPDase, alkaline phosphatase, and adenosine deaminase circulate in human vitreous. Purinergic enzymes are up-regulated in diabetic eyes with vitreous hemorrhage. Soluble adenylate kinase maintains high ATP levels in diabetic retinopathy eyes. Ecto-nucleotidases are co-expressed in the human retina and optic nerve head. Alkaline phosphatase is expressed on neovascular tissues excised from diabetic eyes.
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http://dx.doi.org/10.1007/s00109-018-01734-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6394560PMC
March 2019

Lymphatic Vascular Structures: A New Aspect in Proliferative Diabetic Retinopathy.

Int J Mol Sci 2018 Dec 13;19(12). Epub 2018 Dec 13.

Research Programs Unit, Genome-Scale Biology, Biomedicum Helsinki, University of Helsinki, FI-00014 Helsinki, Finland.

Diabetic retinopathy (DR) is the most common diabetic microvascular complication and major cause of blindness in working-age adults. According to the level of microvascular degeneration and ischemic damage, DR is classified into non-proliferative DR (NPDR), and end-stage, proliferative DR (PDR). Despite advances in the disease etiology and pathogenesis, molecular understanding of end-stage PDR, characterized by ischemia- and inflammation-associated neovascularization and fibrosis, remains incomplete due to the limited availability of ideal clinical samples and experimental research models. Since a great portion of patients do not benefit from current treatments, improved therapies are essential. DR is known to be a complex and multifactorial disease featuring the interplay of microvascular, neurodegenerative, metabolic, genetic/epigenetic, immunological, and inflammation-related factors. Particularly, deeper knowledge on the mechanisms and pathophysiology of most advanced PDR is critical. Lymphatic-like vessel formation coupled with abnormal endothelial differentiation and progenitor cell involvement in the neovascularization associated with PDR are novel recent findings which hold potential for improved DR treatment. Understanding the underlying mechanisms of PDR pathogenesis is therefore crucial. To this goal, multidisciplinary approaches and new ex vivo models have been developed for a more comprehensive molecular, cellular and tissue-level understanding of the disease. This is the first step to gain the needed information on how PDR can be better evaluated, stratified, and treated.
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http://dx.doi.org/10.3390/ijms19124034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321212PMC
December 2018

Repair of primary RRD - comparing pars plana vitrectomy procedure with combined phacovitrectomy with standard foldable intraocular lens implantation.

Clin Ophthalmol 2018 15;12:1449-1457. Epub 2018 Aug 15.

Department of Public Health, University of Helsinki, Helsinki, Finland.

Background: Pars plana vitrectomy (PPV) combined with phacoemulsification and primary intraocular lens implantation can be performed for the repair of primary rhegmatogenous retinal detachment (RRD; PHACOVIT group). The safety and efficacy of this combined ophthalmic procedure on RRD surgery outcomes remain unclear compared with more conventional PPV technique alone (VITRET group). We explored the need for reoperation after primary surgical procedure in these two groups.

Methods: Retrospective, longitudinal, register-based cohort of RRD patients was operated in University Eye Clinic, Helsinki, Finland, during 2008-2014. The main outcome measure was reoperation rate during a postoperative follow-up period of 1 year due to retinal re-detachment, vitreous rehemorrhage, postoperative endophthalmitis, secondary pucker, macular hole or other reasons.

Results: We analyzed 1,690 consecutive RRD cases, out of which 1,564 patients were treated in the PPV VITRET group and 126 patients in the PHACOVIT-operated group. Risk for reoperation was 2.67 times higher in the PHACOVIT group compared to the PPV VITRET group (95% CI 1.85-3.85).

Conclusion: The reoperation rate was higher in RRD eyes operated with combined cataract surgery plus PPV, suggesting that RRD eyes should not primarily undergo combined PHACOVIT surgery.
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http://dx.doi.org/10.2147/OPTH.S171451DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6101008PMC
August 2018

Systems pathology analysis identifies neurodegenerative nature of age-related vitreoretinal interface diseases.

Aging Cell 2018 Oct 2;17(5):e12809. Epub 2018 Jul 2.

Institute of Biotechnology and Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland.

Aging is a phenomenon that is associated with profound medical implications. Idiopathic epiretinal membrane (iEMR) and macular hole (MH) are the major vision-threatening vitreoretinal diseases affecting millions of aging people globally, making these conditions an important public health issue. iERM is characterized by fibrous tissue developing on the surface of the macula, which leads to biomechanical and biochemical macular damage. MH is a small breakage in the macula and is associated with many ocular conditions. Although several individual factors and pathways are suggested, a systems pathology level understanding of the molecular mechanisms underlying these disorders is lacking. Therefore, we performed mass spectrometry-based label-free quantitative proteomics analysis of the vitreous proteomes from patients with iERM and MH to identify the key proteins, as well as the multiple interconnected biochemical pathways, contributing to the development of these diseases. We identified a total of 1,014 unique proteins, many of which are linked to inflammation and the complement cascade, revealing the inflammation processes in retinal diseases. Additionally, we detected a profound difference in the proteomes of iEMR and MH compared to those of diabetic retinopathy with macular edema and rhegmatogenous retinal detachment. A large number of neuronal proteins were present at higher levels in the iERM and MH vitreous, including neuronal adhesion molecules, nervous system development proteins, and signaling molecules, pointing toward the important role of neurodegenerative component in the pathogenesis of age-related vitreoretinal diseases. Despite them having marked similarities, several unique vitreous proteins were identified in both iERM and MH, from which candidate targets for new diagnostic and therapeutic approaches can be provided.
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http://dx.doi.org/10.1111/acel.12809DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156470PMC
October 2018

The microenvironment of proliferative diabetic retinopathy supports lymphatic neovascularization.

J Pathol 2018 06 6;245(2):172-185. Epub 2018 Apr 6.

Research Programmes Unit, Genome-Scale Biology, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.

Proliferative diabetic retinopathy (PDR) is a major diabetic microvascular complication characterized by pathological angiogenesis. Several retinopathy animal models have been developed to study the disease mechanisms and putative targets. However, knowledge on the human proliferative disease remains incomplete, relying on steady-state results from thin histological neovascular tissue sections and vitreous samples. New translational models are thus required to comprehensively understand the disease pathophysiology and develop improved therapeutic interventions. We describe here a clinically relevant model, whereby the native multicellular PDR landscape and neo(fibro)vascular processes can be analysed ex vivo and related to clinical data. As characterized by three-dimensional whole-mount immunofluorescence and electron microscopy, heterogeneity in patient-derived PDR neovascular tissues included discontinuous capillaries coupled with aberrantly differentiated, lymphatic-like and tortuous endothelia. Spatially confined apoptosis and proliferation coexisted with inflammatory cell infiltration and unique vascular islet formation. Ex vivo-cultured explants retained multicellularity, islet patterning and capillary or fibrotic outgrowth in response to vitreoretinal factors. Strikingly, PDR neovascular tissues, whose matched vitreous samples enhanced lymphatic endothelial cell sprouting, contained lymphatic-like capillaries in vivo and developed Prox1 capillaries and sprouts with lymphatic endothelial ultrastructures ex vivo. Among multiple vitreal components, vascular endothelial growth factor C was one factor found at lymphatic endothelium-activating concentrations. These results indicate that the ischaemia-induced and inflammation-induced human PDR microenvironment supports pathological neolymphovascularization, providing a new concept regarding PDR mechanisms and targeting options. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/path.5070DOI Listing
June 2018

Statin use and vitreoretinal surgery: Findings from a Finnish population-based cohort study.

Acta Ophthalmol 2018 Aug 16;96(5):442-451. Epub 2018 Jan 16.

Department of Public Health, University of Helsinki, Helsinki, Finland.

Purpose: Vitreoretinal (VR) surgery is the third most common intraocular surgery after refractive and cataract surgery. The impact of statin therapy on VR surgery outcomes remains unclear, despite a potentially beneficial effect. We explored the association of preoperative statin therapy and the need for revitrectomy after primary vitrectomy.

Methods: Our historical, population-based, register-based, VR surgery cohort consisted of 5709 patients operated in a tertiary, academic referral hospital in Finland, during 2008-2014, covering 6.5 years. Subgroup analysis was performed as follows: eyes operated due to (i) rhegmatogenous retinal detachment (RRD), (ii) VR interface diseases (macular pucker/hole), (iii) diabetic maculopathy or proliferative retinopathy, (iv) vitreous haemorrhage, (v) lens subluxation, (vi) vitreous opacities or (vii) other VR indication. The primary end-point event was revitrectomy during a postoperative follow-up period of 1 year due to retinal redetachment, vitreous rehaemorrhage, postoperative endophthalmitis, recurrent pucker or unclosed macular hole.

Results: Rhegmatogenous retinal detachment (RRD) was the second most frequent indication of VR surgery, including 1916 patients, with 305 re-operations with rate 0.20 (95% CI 0.18-0.23) per person-year. Statin treatment in time of operation was associated with lower risk of re-operation according to relative scale (incidence rate ratio 0.72, 95% CI 0.53-0.97), but not in absolute scale (incidence rate difference -0.58, 95% CI -4.30 to 3.15 for 100 person-years). No association with statin therapy and vitrectomy outcome was observed in the other VR subgroups.

Conclusion: Use of statin treatment was associated with a 28% lower risk of revitrectomy in patients operated due to RRD. Further randomized clinical trials are highly warranted.
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http://dx.doi.org/10.1111/aos.13641DOI Listing
August 2018

A retrospective study comparing outcomes of primary rhegmatogenous retinal detachment repair by scleral buckling and pars plana vitrectomy in Finland.

Clin Ophthalmol 2017 10;11:503-509. Epub 2017 Mar 10.

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

Background: Rhegmatogenous retinal detachment (RRD) is the most common form of retinal detachment and an ophthalmic emergency. Here, we compared outcomes of primary RRD eyes operated with conventional scleral buckling (SB) with cryoretinopexy to those operated with standard pars plana vitrectomy (PPV).

Methods: This is an institutional, retrospective, register-based, observational, comparative study. Based on the surgical procedure, 319 eyes of 319 patients were divided into two groups: SB plus cryotherapy (n=50) and PPV (n=269). Changes in intraocular pressure (IOP) and best-corrected visual acuity (BCVA) were recorded at 30 days and reoperation rates within 180 days postoperatively.

Results: Eyes operated with PPV had less reoperations within the first 180 days as compared with SB eyes (=0.001, log-rank test); however, changes in IOP were more prominent (mean ± standard deviation: +8.1±8.8 vs. +4.4±7.0 mmHg, respectively; =0.006). Changes in BCVA did not differ between the surgical procedures.

Conclusion: PPV was associated with higher primary anatomic success rates and lower risk of reoperation but significant IOP elevation when compared to SB. These factors should be case-specifically considered when choosing treatment modality for primary RRD.
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http://dx.doi.org/10.2147/OPTH.S128746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5354527PMC
March 2017

NLRP3 inflammasome activation is associated with proliferative diabetic retinopathy.

Acta Ophthalmol 2017 Dec 8;95(8):803-808. Epub 2017 Mar 8.

School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland.

Purpose: Innate immunity and dysregulation of inflammatory processes play a role in vascular diseases like atherosclerosis or diabetes. Nucleotide-binding domain and Leucine-rich repeat Receptor containing a Pyrin domain 3 (NLRP3) inflammasomes are pro-inflammatory signalling complexes that were found in 2002. In addition to pathogens and other extracellular threats, they can be activated by various endogenous danger signals. The purpose of this study was to find out whether NLRP3 activation occurs in patients with sight-threatening forms of diabetic retinopathy (DR).

Methods: Inflammasome components NLRP3 and caspase-1, inflammasome-related pro-inflammatory cytokines IL-1β and IL-18, vascular endothelial growth factor (VEGF), acute-phase cytokines TNF-α and IL-6, as well as adaptive immunity-related cytokine interferon gamma (IFN-γ) were measured from the vitreous samples of 15 non-proliferative diabetic retinopathy (non-PDR) and 23 proliferative diabetic retinopathy (PDR) patients using the enzyme-linked immunosorbent assay (ELISA) method. The adaptor protein apoptosis-associated speck-like protein containing a CARD (ASC) was determined using the Western blot technique.

Results: Inflammasome components were present in the vitreous of DR patients. Along with VEGF, the levels of caspase-1 and IL-18 were significantly increased, especially in PDR eyes. Interestingly, clearly higher levels of NLRP3 were found in the PDR eyes with tractional retinal detachment (TRD) than from PDR eyes with fully attached retina. There were no significant differences in the amounts of IL-1β, TNF-α, IL-6, and IFN-γ that were detectable in the vitreous of both non-PDR and PDR patients.

Conclusion: Our results suggest that NLRP3 inflammasome activation can be associated especially with the pathogenesis of PDR. The lack of differences in TNF-α, IL-6, and IFN-γ also alludes that acute inflammation or T-cell-mediated responses do not dominate in PDR pathogenesis.
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http://dx.doi.org/10.1111/aos.13427DOI Listing
December 2017

Elevated Levels of Plasma IgA Autoantibodies against Oxidized LDL Found in Proliferative Diabetic Retinopathy but Not in Nonproliferative Retinopathy.

J Diabetes Res 2016 20;2016:2614153. Epub 2016 Dec 20.

PEDEGO Research Unit, Department of Ophthalmology, Medical Research Center (MRC Oulu), Oulu University Hospital and University of Oulu, Oulu, Finland; Research Unit of Internal Medicine, Medical Research Center Oulu (MRC Oulu), Oulu University Hospital and University of Oulu, Oulu, Finland.

. This study investigated the association of autoantibodies binding to oxidized low-density lipoproteins (oxLDL) in diabetic retinopathy (DR). . Plasma from 229 types 1 and 2 patients with DR including diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) was analysed with ELISA-based assay to determine IgA, IgG, and IgM autoantibody levels binding to oxLDL. The controls were 106 diabetic patients without retinopathy (NoDR) and 139 nondiabetic controls (C). . PDR group had significantly higher IgA autoantibody levels than DME or NoDR: mean 94.9 (SD 54.7) for PDR, 75.5 (41.8) for DME ( = 0.001), and 76.1 (48.2) for NoDR ( = 0.008). There were no differences in IgG, IgM, or IgA that would be specific for DR or for DME. Type 2 diabetic patients had higher levels of IgA autoantibodies than type 1 diabetic patients (86.0 and 65.5, resp., = 0.004) and the highest levels in IgA were found in type 2 diabetic patients with PDR (119.1, > 0.001). . IgA autoantibodies were increased in PDR, especially in type 2 diabetes. The high levels of IgA in PDR, and especially in type 2 PDR patients, reflect the inflammatory process and enlighten the role of oxLDL and its autoantibodies in PDR.
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http://dx.doi.org/10.1155/2016/2614153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5206457PMC
May 2017

Deregulation of ocular nucleotide homeostasis in patients with diabetic retinopathy.

J Mol Med (Berl) 2017 02 16;95(2):193-204. Epub 2016 Sep 16.

MediCity Research Laboratory and Department of Medical Microbiology and Immunology, University of Turku, Tykistökatu 6A, 20520, Turku, Finland.

Clear signaling roles for ATP and adenosine have been established in all tissues, including the eye. The magnitude of signaling responses is governed by networks of enzymes; however, little is known about the regulatory mechanisms of purinergic signaling in the eye. By employing thin-layer chromatographic assays with H-labeled substrates, this study aimed to evaluate the role of nucleotide homeostasis in the pathogenesis of vitreoretinal diseases in humans. We have identified soluble enzymes ecto-5'-nucleotidase/CD73, adenylate kinase-1, and nucleoside diphosphate kinase in the vitreous fluid that control active cycling between pro-inflammatory ATP and anti-inflammatory adenosine. Strikingly, patients with proliferative form of diabetic retinopathy (DR) had higher adenylate kinase activity and ATP concentration, when compared to non-proliferative DR eyes and non-diabetic controls operated for rhegmatogenous retinal detachment, macular hole, and pucker. The non-parametric correlation analysis revealed positive correlations between intravitreal adenylate kinase and concentrations of ATP, ADP, and other angiogenic (angiopoietins-1 and -2), profibrotic (transforming growth factor-β1), and proteolytic (matrix metalloproteinase-9) factors but not erythropoietin and VEGF. Immunohistochemical staining of postmortem human retina additionally revealed selective expression of ecto-5'-nucleotidase/CD73 on the rod-and-cone-containing photoreceptor cells. Collectively, these findings provide novel insights into the regulatory mechanisms that influence purinergic signaling in diseased eye and open up new possibilities in the development of enzyme-targeted therapeutic approaches for prevention and treatment of DR.

Key Message: Ecto-5'-nucleotidase/CD73 and adenylate kinase-1 circulate in human vitreous fluid. Adenylate kinase activity is high in diabetic eyes with proliferative retinopathy. Diabetic eyes display higher intravitreal ATP/ADP ratio than non-diabetic controls. Soluble adenylate kinase maintains resynthesis of inflammatory ATP in diabetic eyes.
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http://dx.doi.org/10.1007/s00109-016-1472-6DOI Listing
February 2017

Statin medication in patients with epiretinal membrane is associated with low intravitreal EPO, TGF-beta-1, and VEGF levels.

Clin Ophthalmol 2016 23;10:921-8. Epub 2016 May 23.

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

Background: In eyes with idiopathic epiretinal membrane (iERM), the intravitreal growth factor and cytokine levels may associate with postvitrectomy outcomes. Here, we have analyzed the perioperative intravitreal protein levels of potent vasoactive, proinflammatory, and extracellular matrix-remodeling factors in iERM eyes and evaluated the postvitrectomy outcomes.

Methods: This was an institutional, observational study. Eyes operated on for iERM (n=26) were analyzed according to the use of statin medication. Vitreous samples were subjected to protein measurements of angiopoietin-1 and -2, erythropoietin, transforming growth factor-β1, and vascular endothelial growth factor by enzyme-linked immunosorbent assay, and of matrix metalloproteinase-2 and -9 by gelatin zymography. One-month visual outcomes and 1-year revitrectomy rates were recorded.

Results: In iERM eyes of patients taking statins, intravitreal levels of erythropoietin (mean ± standard deviation, 10.8±4.9 vs 82.9±119.5 mIU/mg, P=0.003), transforming growth factor-β1 (2.3±4.7 vs 15.8±16.3 pg/mg, P=0.035), and vascular endothelial growth factor (5.5±9.9 vs 236.6±491.6 pg/mg, P=0.006) were lower than in nonstatin-treated patients. At 1-month, visual gain did not significantly differ between iERM eyes of patients with statins and those without (improvement 0.27±0.20 vs 0.16±0.38 logarithm of the minimum angle of resolution units, P=0.118).

Conclusion: Systemic statin therapy might have a favorable effect on intravitreal factors involved in vascular permeability, inflammation, and fibroproliferation in aging human iERM eyes.
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http://dx.doi.org/10.2147/OPTH.S105686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4883812PMC
June 2016

Simvastatin use associated with low intraocular ADP levels in patients with sight-threatening diabetic retinopathy.

Graefes Arch Clin Exp Ophthalmol 2016 Aug 15;254(8):1643-1644. Epub 2016 Apr 15.

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

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http://dx.doi.org/10.1007/s00417-016-3349-3DOI Listing
August 2016

Quantitative Proteomics Analysis of Vitreous Humor from Diabetic Retinopathy Patients.

J Proteome Res 2015 Dec 30;14(12):5131-43. Epub 2015 Oct 30.

Molecular Systems Biology Research Group, Institute of Biotechnology, University of Helsinki , FI-00014 Helsinki, Finland.

Initial triggers for diabetic retinopathy (DR) are hyperglycemia-induced oxidative stress and advanced glycation end-products. The most pathological structural changes occur in retinal microvasculature, but the overall development of DR is multifactorial, with a complex interplay of microvascular, neurodegenerative, genetic/epigenetic, immunological, and secondary inflammation-related factors. Although several individual factors and pathways have been associated with retinopathy, a systems level understanding of the disease is lacking. To address this, we performed mass spectrometry based label-free quantitative proteomics analysis of 138 vitreous humor samples from patients with nonproliferative DR or the more severe proliferative form of the disease. Additionally, we analyzed samples from anti-VEGF (vascular endothelial growth factor) (bevacizumab)-treated patients from both groups. In our study, we identified 2482 and quantified the abundancy of 1351 vitreous proteins. Of these, the abundancy of 230 proteins was significantly higher in proliferative retinopathy compared with nonproliferative retinopathy. This specific subset of proteins was linked to inflammation, complement, and coagulation cascade proteins, protease inhibitors, apolipoproteins, immunoglobulins, and cellular adhesion molecules, reflecting the multifactorial nature of the disease. The identification of the key molecules of the disease is critical for the development of new therapeutic molecules and for the new use of existing drugs.
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http://dx.doi.org/10.1021/acs.jproteome.5b00900DOI Listing
December 2015

Improved outcome after primary vitrectomy in diabetic patients treated with statins.

Eur J Ophthalmol 2016 Mar-Apr;26(2):174-81. Epub 2015 Aug 26.

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

Purpose: To evaluate the effect of preoperative statin treatment on the outcome of primary vitrectomy in type 1 and 2 diabetic patients.

Methods: In this open, observational institutional study, a total of 192 eyes of 171 type 1 and 2 adult diabetic patients admitted for primary vitrectomy for management of sight-threatening forms of diabetic retinopathy were divided according to the use of lipid-lowering therapy: those with statin treatment (79 eyes of 73 patients) and those taking no statin medication (113 eyes of 98 patients). One-month best-corrected visual acuity (BCVA) gain and cumulative 12-month revitrectomy frequency were analyzed.

Results: In multivariate linear regression, diabetic patients with statin treatment had a better 1-month BCVA improvement than did those without statin treatment (absolute difference 0.26, 95% confidence interval [CI] 0.02-0.50, p = 0.028). Subgroup analysis revealed that diabetic patients on statin had better postoperative BCVA improvement when preoperative status included partial or panretinal laser photocoagulation (p = 0.042 and p = 0.049) and anti-vascular endothelial growth factor therapy (p = 0.011). Moreover, diabetic patients with preoperative macular edema (p = 0.009), vitreous hemorrhage (p<0.001), proliferative retinopathy (p<0.001), or tractional retinal detachment (p = 0.010) had better BCVA recovery if receiving statin. In Cox proportional hazards regression model, revitrectomies in our 12-month follow-up were less frequent in diabetic patients on statin treatment (hazard ratio 0.28, 95% CI 0.08-0.93, p = 0.037).

Conclusions: These data provide novel insight into the potential clinical benefit for patients with sight-threatening diabetic retinopathy undergoing vitrectomy treated with statin.
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http://dx.doi.org/10.5301/ejo.5000657DOI Listing
June 2016

A Case of Abnormal Lymphatic-Like Differentiation and Endothelial Progenitor Cell Activation in Neovascularization Associated with Hemi-Retinal Vein Occlusion.

Case Rep Ophthalmol 2015 May-Aug;6(2):228-38. Epub 2015 Jul 17.

Genome-Scale Biology Research Program, Research Programs Unit, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.

Purpose: Pathological vascular differentiation in retinal vein occlusion (RVO)-related neovessel formation remains poorly characterized. The role of intraocular lymphatic-like differentiation or endothelial progenitor cell activity has not been studied in this disease.

Methods: Vitrectomy was performed in an eye with hemi-RVO; the neovessel membrane located at the optic nerve head was removed and subjected to immunohistochemistry. Characterization of the neovascular tissue was performed using hematoxylin and eosin, α-smooth muscle actin, and the pan-endothelial cell (EC) adhesion molecule CD31. The expression of lymphatic EC markers was studied by lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1), podoplanin (PDPN), and prospero-related homeobox protein 1 (Prox-1). Potential vascular stem/progenitor cells were identified by active cellular proliferation (Ki67) and expression of the stem cell marker CD117.

Results: The specimen contained blood vessels lined by ECs and surrounded by pericytes. Immunoreactivity for LYVE-1 and Prox-1 was detected, with Prox-1 being more widely expressed in the active Ki67-positive lumen-lining cells. PDPN expression was instead found in the cells residing in the extravascular tissue. Expression of the stem cell markers CD117 and Ki67 suggested vascular endothelial progenitor cell activity.

Conclusions: Intraocular lymphatic-like differentiation coupled with progenitor cell activation may be involved in the pathology of neovessel formation in ischemia-induced human hemi-RVO.
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http://dx.doi.org/10.1159/000437254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4553915PMC
September 2015

Indications of lymphatic endothelial differentiation and endothelial progenitor cell activation in the pathology of proliferative diabetic retinopathy.

Acta Ophthalmol 2015 Sep 21;93(6):512-23. Epub 2015 Apr 21.

Research Programs Unit, Genome-Scale Biology, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.

Purpose: Proliferative diabetic retinopathy (PDR) is characterized by ischaemia- and inflammation-induced neovascularization, but the pathological vascular differentiation in PDR remains poorly characterized. Here, endothelial progenitor and growth properties, as well as potential lymphatic differentiation, were investigated in the neovascular membrane specimens from vitrectomized patients with PDR.

Methods: The expression of pan-endothelial CD31 (PECAM-1), ETS-related gene (ERG), α-smooth muscle actin (α-SMA), and stem/progenitor cell marker CD117 (c-kit) and cell proliferation marker Ki67 was investigated along with the markers of lymphatic endothelial differentiation (vascular endothelial growth factor receptor (VEGFR)-3; prospero-related homeobox gene-1 (Prox-1), lymphatic vessel endothelial receptor [LYVE)-1 and podoplanin (PDPN)] by immunohistochemistry. Lymphocyte antigen CD45 and pan-macrophage marker CD68 were likewise investigated.

Results: All specimens displayed CD31, ERG and α-SMA immunoreactivity in irregular blood vessels. Unexpectedly, VEGFR3 and Prox-1 lymphatic marker positive vessels were also detected in several tissues. Prox-1 was co-expressed with CD117 in lumen-lining endothelial cells and adjacent cells, representing putative endothelial stem/progenitor cells and pro-angiogenic perivascular cells. Immunoreactivity of CD45 and CD68 was detectable in all investigated diabetic neovessel specimens. PDPN immunoreactivity was also detected in irregular lumen-forming structures, but these cells lacked CD31 and ERG that mark blood and lymphatic endothelium.

Conclusions: Although the inner part of human eye is physiologically devoid of lymphatic vessels, lymphatic differentiation associated with endothelial stem/progenitor cell activation may be involved in the pathogenesis of human PDR. Further studies are warranted to elucidate whether targeting lymphatic factors could be beneficial in the treatment of patients with the sight-threatening forms of DR.
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http://dx.doi.org/10.1111/aos.12741DOI Listing
September 2015

Statins in rhegmatogenous retinal detachment are associated with low intravitreal angiopoietin-2, VEGF and MMP-2 levels, and improved visual acuity gain in vitrectomized patients.

Graefes Arch Clin Exp Ophthalmol 2015 Oct 30;253(10):1685-93. Epub 2014 Nov 30.

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

Purpose: In rhegmatogenous retinal detachment (RRD), intravitreal growth factors and cytokines may compromise post-vitrectomy outcomes. Here, we analysed perioperative intravitreal protein levels of potent vasoactive, pro-inflammatory, and extracellular matrix-remodelling factors in RRD eyes of patients treated with statins and evaluated post-vitrectomy outcome in the same study eyes.

Methods: Institutional, retrospective, observational study of 14 patients operated on for RRD while on statins compared to patients without statin medication (n = 82). Vitreous samples were subjected to protein measurements of angiopoietin (ANGPT)-1 and -2, transforming growth factor-β1, and vascular endothelial growth factor (VEGF) by ELISA, and of matrix metalloproteinase (MMP)-2 and -9 by gelatin zymography. A 1-month best-corrected visual acuity (BCVA) gain was modelled by Student's T-test and multivariate linear regression with concomitant perioperative medication. Cumulative 12-month revitrectomy frequency was modelled by Kaplan-Meier log-rank test.

Results: Intravitreal levels of ANGPT-2 (49.2 ± 33.1 vs. 112.8 ± 134.1 pg/ml, mean ± SD, p < 0.001), VEGF (2.3 ± 2.4 vs. 17.7 ± 57.8 pg/ml, p = 0.021), and MMP-2 (1107.1 ± 884.6 vs 1976.4 ± 970.1 AU/ml, p = 0.005) in RRD eyes of patients treated with statins were lower than in non-statin-treated controls. Patients on statins had better 1-month BCVA improvement than did those not on statins (p = 0.022), with no difference in 1-year re-vitrectomy rates.

Conclusions: Intravitreal levels of ANGPT-2, VEGF, factors involved in vascular permeability and inflammation, and activity of MMP-2, the factor connected with breakdown of basement membrane and fibroproliferation, were lower in RRD eyes of patients with statin treatment. At 1-month, postoperative BCVA gain was improved in statin-treated RRD eyes, suggesting that statin administration may be effective in preventing inflammation-related PVR formation.
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http://dx.doi.org/10.1007/s00417-014-2873-2DOI Listing
October 2015

Increased intravitreal adenosine 5'-triphosphate, adenosine 5'-diphosphate and adenosine 5'-monophosphate levels in patients with proliferative diabetic retinopathy.

Acta Ophthalmol 2015 Feb 30;93(1):67-73. Epub 2014 Jul 30.

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

Purpose: Extracellular purines play important role in ocular physiology, diabetes, vascular remodelling and adaptation to inflammation. This study was aimed to evaluate intravitreal purine levels in patients with diabetic retinopathy (DR) and other non-vascular vitreoretinal eye diseases.

Methods: Vitreous samples were collected at the start of the three-port pars plana vitrectomy. Study group comprised 55 eyes operated due to sight-threatening forms of DR, including eyes of 24 patients with proliferative DR. Of the 143 non-diabetic controls, 112 had rhegmatogenous retinal detachment and 31 macular hole or pucker. Intravitreal purine concentrations were determined using a combination of bioluminescent [adenosine 5'-triphosphate (ATP), adenosine 5'-diphosphate (ADP)] and fluorometric [adenosine 5'-monophosphate (AMP), adenosine, inosine] enzyme-coupled sensing assays.

Results: Compared with non-diabetic controls, DR eyes contained significantly higher (p < 0.01) concentrations of ATP (4.2 ± 0.6 versus 34.5 ± 13.7 nm; mean ± SEM), ADP (19.5 ± 2.7 versus 43.7 ± 14.5 nm) and AMP (1290 ± 115 versus 1876 ± 190 nm). Intravitreal adenosine and inosine levels varied within submicromolar to low micromolar range, and their concentrations did not differ between the groups studied.

Conclusions: High concentrations of intravitreal nucleotides ATP, ADP and AMP may be related to the pathogenesis of sight-threatening forms of DR.
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http://dx.doi.org/10.1111/aos.12507DOI Listing
February 2015

Poor glycemic control associates with high intravitreal angiopoietin-2 levels in patients with diabetic retinopathy.

Acta Ophthalmol 2015 Sep 2;93(6):e515-6. Epub 2014 Apr 2.

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

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http://dx.doi.org/10.1111/aos.12401DOI Listing
September 2015

Low intravitreal angiopoietin-2 and VEGF levels in vitrectomized diabetic patients with simvastatin treatment.

Acta Ophthalmol 2014 Nov 8;92(7):675-81. Epub 2014 Feb 8.

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

Purpose: To investigate the intravitreal levels of potent vasoactive, angiogenic and extracellular matrix remodelling factors in the diabetic patients with simvastatin treatment.

Methods: This is an institutional, prospective, observational case-control study. Type-1 and type-2 diabetic patients on lipophilic simvastatin (N = 14) compared with patients without statin medication (N = 50). Vitreous samples were subjected to protein measurements of angiopoietin (Ang)-1 and Ang-2, erythropoietin (EPO), transforming growth factor (TGF)-β1, vascular endothelial growth factor (VEGF) by ELISA and matrix metalloproteinase (MMP)-2 and MMP-9 by gelatin zymography.

Results: Intravitreal levels of Ang-2 (p = 0.029), VEGF (p = 0.001) and proMMP-9 (p = 0.015) were lower in simvastatin-treated than in non-statin-treated controls. In diabetics with macular oedema (DME), intravitreal Ang-2 (p = 0.006) and VEGF (p = 0.002) levels were lower in simvastatin-treated patients compared with non-statin-treated controls. In those patients with proliferative diabetic retinopathy (PDR), intravitreal Ang-2 (p = 0.002), TGF-β1 (p = 0.037), VEGF (p = 0.001) and pro- and totalMMP-9 (p = 0.004 and p = 0.007) levels were lower when receiving simvastatin medication.

Conclusions: In diabetic patients with DME or PDR, the intravitreal levels of permeability and proangiogenic factors Ang-2 and VEGF were lower in simvastatin-treated than in those without statin medication. Moreover, the levels of MMP-9 and TGF-β1, factors involved in the breakdown of basement membrane and fibroproliferation, were lower in patients with PDR having simvastatin medication. When acetylsalicylic acid was combined with simvastatin treatment, the intraocular levels of Ang-2 and VEGF were significantly lower than in diabetics treated with simvastatin alone. These data provide a novel insight into the potential protective mechanisms underlying simvastatin medication in patients with diabetic retinopathy complications.
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http://dx.doi.org/10.1111/aos.12363DOI Listing
November 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.
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http://dx.doi.org/10.1007/s00417-013-2508-zDOI Listing
June 2014

Increased intravitreal angiopoietin-2 levels in patients with retinal vein occlusion.

Acta Ophthalmol 2014 Mar 21;92(2):e164-5. Epub 2013 Jun 21.

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

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http://dx.doi.org/10.1111/aos.12223DOI Listing
March 2014