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  • Ylinen, Petteri; Holmstrom, Emil; Laine, Ilkka; Lindholm, Juha-Matti; Tuuminen, Raimo (2018)
    PurposeTo examine the anti-inflammatory efficacy and tolerance between preservative-free dexamethasone (DEX) and diclofenac (DICL) eye drops, and their combination following cataract surgery. MethodsA randomized, double-blind, prospective single-centre study with 189 eyes of 180 patients undergoing routine cataract surgery. Laser flare meter measurement and spectral-domain optical coherence tomography imaging were conducted before surgery and at the 28-day postoperative visit. Clinical characteristics, surgical parameters and assessment of postoperative symptoms were recorded. ResultsPreoperative flare was 9.00.6pu/ms and central retinal thickness (CRT) 269.6 +/- 1.9m (mean +/- SEM). On day 28, flare was 22.1 +/- 2.9 pu/ms for DEX, 17.4 +/- 2.5pu/ms for DICL and 13.0 +/- 1.6pu/ms (p ConclusionDiclofenac (DICL), as well as the combination of DEX and DICL, were superior to DEX monotherapy in minimizing CRT change and the incidence of PCME. Combination medication showed no added value compared to DICL monotherapy in uneventful cataract surgery.
  • Munier, Francis L.; Beck-Popovic, Maja; Chantada, Guillermo L.; Cobrinik, David; Kivelä, Tero T.; Lohmann, Dietmar; Maeder, Philippe; Moll, Annette C.; Carcaboso, Angel Montero; Moulin, Alexandre; Schaiquevich, Paula; Bergin, Ciara; Dyson, Paul J.; Houghton, Susan; Puccinelli, Francesco; Vial, Yvan; Gaillard, Marie-Claire; Stathopoulos, Christina (2019)
    Retinoblastoma is lethal by metastasis if left untreated, so the primary goal of therapy is to preserve life, with ocular survival, visual preservation and quality of life as secondary aims. Historically, enucleation was the first successful therapeutic approach to decrease mortality, followed over 100 years ago by the first eye salvage attempts with radiotherapy. This led to the empiric delineation of a window for conservative management subject to a "state of metastatic grace" never to be violated. Over the last two decades, conservative management of retinoblastoma witnessed an impressive acceleration of improvements, culminating in two major paradigm shifts in therapeutic strategy. Firstly, the introduction of systemic chemotherapy and focal treatments in the late 1990s enabled radiotherapy to be progressively abandoned. Around 10 years later, the advent of chemotherapy in situ, with the capitalization of new routes of targeted drug delivery, namely intra-arterial, intravitreal and now intracameral injections, allowed significant increase in eye preservation rate, definitive eradication of radiotherapy and reduction of systemic chemotherapy. Here we intend to review the relevant knowledge susceptible to improve the conservative management of retinoblastoma in compliance with the "state of metastatic grace", with particular attention to (i) reviewing how new imaging modalities impact the frontiers of conservative management, (ii) dissecting retinoblastoma genesis, growth patterns, and intraocular routes of tumor propagation, (iii) assessing major therapeutic changes and trends, (iv) proposing a classification of relapsing retinoblastoma, (v) examining treatable/preventable disease-related or treatment-induced complications, and (vi) appraising new therapeutic targets and concepts, as well as liquid biopsy potentiality.
  • Kanclerz, Piotr; Khoramnia, Ramin; Wang, Xiaogang (2021)
    Introduction: Accurate assessment of the corneal shape is important in cataract and refractive surgery, both in screening of candidates as well as for analyzing postoperative outcomes. Although corneal topography and tomography are widely used, it is common that these technologies are confused. The aim of this study was to present the current developments of these technologies and particularly distinguish between corneal topography and tomography. Methods: The PubMed, Web of Science and Embase databases were the main resources used to investigate the medical literature. The following keywords were used in various combinations: cornea, corneal, topography, tomography, Scheimpflug, Pentacam, optical coherence tomography. Results: Topography is the study of the shape of the corneal surface, while tomography allows a three-dimensional section of the cornea to be presented. Corneal topographers can be divided into large- and small-cone Placido-based devices, as well as devices with color-LEDs. For corneal tomography, scanning slit or Scheimpflug imaging and optical coherence tomography may be employed. In several devices, corneal topography and tomography have been successfully combined with tear-film analysis, aberrometry, optical biometry and anterior/posterior segment optical coherence tomography. Conclusion: There is a wide variety of imaging techniques to obtain corneal power maps. As different technologies are used, it is imperative that doctors involved in corneal surgery understand the science and clinical application of devices for corneal evaluation in depth.
  • Shakirova, Julia R.; Sadeghi, Amir; Koblova, Alla A.; Chelushkin, Pavel S.; Toropainen, Elisa; Tavakoli, Shirin; Kontturi, Leena-Stiina; Lajunen, Tatu; Tunik, Sergey P.; Urtti, Arto (2020)
    Two iridium [Ir(NC)(2)(NN)](+) complexes with the diimine NN ligand containing a long polymethylene hydrophobic chain were synthesized and characterized by using NMR and ESI mass-spectrometry: NN - 2-(1-hexadecyl-1H-imidazol-2-yl)pyridine, NC - methyl-2-phenylquinoline-4-carboxylate (Ir1) and 2-phenylquinoline-4-carboxylic acid (Ir2). These complexes were used to prepare the luminescent PEGylated DPPC liposomes (DPPC/DSPE-PEG2000/Ir-complex = 95/4.5/1 mol%) using a thin film hydration method. The narrowly dispersed liposomes had diameters of about 110 nm. The photophysics of the complexes and labeled liposomes were carefully studied. Ir1 and Ir2 give red emission (lambda(em) = 667 and 605 nm) with a lifetime in the microsecond domain and quantum yields of 4.8% and 10.0% in degassed solution. Incorporation of the complexes into the liposome lipid bilayer results in shielding of the emitters from interaction with molecular oxygen and partial suppression of excited state nonradiative relaxation due to the effect of the relatively rigid bilayer matrix. Delivery of labeled liposomes to the cultured ARPE-19 cells demonstrated the usefulness of Ir1 and Ir2 in cellular imaging. Labeled liposomes were then injected intravitreally into rat eyes and imaged successfully with optical coherence tomography and funduscopy. In conclusion, iridium complexes enabled the successful labeling and imaging of liposomes in cells and animals.
  • Lindholm, Vivian; Raita-Hakola, Anna-Maria; Annala, Leevi; Salmivuori, Mari; Jeskanen, Leila; Saari, Heikki; Koskenmies, Sari; Pitkänen, Sari; Pölönen, Ilkka; Isoherranen, Kirsi; Ranki, Annamari (2022)
    Several optical imaging techniques have been developed to ease the burden of skin cancer disease on our health care system. Hyperspectral images can be used to identify biological tissues by their diffuse reflected spectra. In this second part of a three-phase pilot study, we used a novel hand-held SICSURFIS Spectral Imager with an adaptable field of view and target-wise selectable wavelength channels to provide detailed spectral and spatial data for lesions on complex surfaces. The hyperspectral images (33 wavelengths, 477-891 nm) provided photometric data through individually controlled illumination modules, enabling convolutional networks to utilise spectral, spatial, and skin-surface models for the analyses. In total, 42 lesions were studied: 7 melanomas, 13 pigmented and 7 intradermal nevi, 10 basal cell carcinomas, and 5 squamous cell carcinomas. All lesions were excised for histological analyses. A pixel-wise analysis provided map-like images and classified pigmented lesions with a sensitivity of 87% and a specificity of 93%, and 79% and 91%, respectively, for non-pigmented lesions. A majority voting analysis, which provided the most probable lesion diagnosis, diagnosed 41 of 42 lesions correctly. This pilot study indicates that our non-invasive hyperspectral imaging system, which involves shape and depth data analysed by convolutional neural networks, is feasible for differentiating between malignant and benign pigmented and non-pigmented skin tumours, even on complex skin surfaces.
  • Kanclerz, Piotr; Tuuminen, Raimo; Khoramnia, Ramin (2021)
    Introduction: Urbanization has caused dramatic changes in lifestyle, and these rapid transitions have led to an increased risk of noncommunicable diseases, such as type 2 diabetes. In terms of cost-effectiveness, screening for diabetic retinopathy is a critical aspect in diabetes management. The aim of this study was to review the imaging modalities employed for retinal examination in diabetic retinopathy screening. Methods: The PubMed and Web of Science databases were the main sources used to investigate the medical literature. An extensive search was performed to identify relevant articles concerning "imaging ", "diabetic retinopathy " and "screening " up to 1 June 2021. Imaging techniques were divided into the following: (i) mydriatic fundus photography, (ii) non-mydriatic fundus photography, (iii) smartphone-based imaging, and (iv) ultrawide-field imaging. A meta-analysis was performed to analyze the performance and technical failure rate of each method. Results: The technical failure rates for mydriatic and non-mydriatic digital fundus photography, smartphone-based and ultrawide-field imaging were 3.4% (95% CI: 2.3-4.6%), 12.1% (95% CI: 5.4-18.7%), 5.3% (95% CI: 1.5-9.0%) and 2.2% (95% CI: 0.3-4.0%), respectively. The rate was significantly different between all analyzed techniques (p < 0.001), and the overall failure rate was 6.6% (4.9-8.3%; I-2 = 97.2%). The publication bias factor for smartphone-based imaging was significantly higher than for mydriatic digital fundus photography and non-mydriatic digital fundus photography (b = -8.61, b = -2.59 and b = -7.03, respectively; p < 0.001). Ultrawide-field imaging studies were excluded from the final sensitivity/specificity analysis, as the total number of patients included was too small. Conclusions: Regardless of the type of the device used, retinal photographs should be taken on eyes with dilated pupils, unless contraindicated, as this setting decreases the rate of ungradable images. Smartphone-based and ultrawide-field imaging may become potential alternative methods for optimized DR screening; however, there is not yet enough evidence for these techniques to displace mydriatic fundus photography.
  • Gucciardo, Erika; Loukovaara, Sirpa; Salven, Petri; Lehti, Kaisa (2018)
    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.
  • Ilveskoski, Lotta; Taipale, Claudia; Holmstrom, Emil J.; Tuuminen, Raimo (2019)
    Background: The purpose of the study was to identify macular edema after cataract surgery in eyes with and without pseudoexfoliation syndrome. The study was a post-hoc analysis of a randomized, double-blind, prospective single-center study. Patients were enrolled between January 2016 and October 2016 as per the national guidelines for the management of cataract in the Department of Ophthalmology, Kymenlaakso Central Hospital, Kotka, Finland. Methods: One hundred and fifty-six eyes of 149 patients undergoing routine cataract surgery. Postoperatively anti-inflammatory medication was either dexamethasone (N = 78) or diclofenac (N = 78). Spectral domain optical coherence tomography imaging and laser flare meter measurement of the anterior chamber were conducted before surgery and at the control visit 28 days postoperatively. Results: Baseline variables were comparable between eyes with pseudoexfoliation syndrome (N = 32) and those without (N = 124), except for intraocular pressure (P = 0.002) and glaucoma medication (P <0.001). In patients having pseudoexfoliation syndrome, central retinal thickness increase (mean +/- standard error of the mean) was 63.3 +/- 35.5 mu m for dexamethasone and 17.6 +/- 5.8 mu m for diclofenac, compared to 28.9 +/- 8.0 mu m (P = NS) and 6.9 +/- 1.3 mu m (P = 0.014) in eyes without pseudoexfoliation syndrome, respectively. Aqueous flare at 28 days was 25.8 +/- 5.4 pu/ms for patients with pseudoexfoliation syndrome and 18.3 +/- 1.8 pu/ms for those without (P = 0.030). Best corrected visual acuity gain and best corrected visual acuity at 28 days were less in patients having pseudoexfoliation syndrome compared to those without (0.39 +/- 0.07 vs 0.59 +/- 0.03 decimals, P = 0.007; and 0.77 +/- 0.06 vs 0.92 +/- 0.03 decimals, P = 0.008, respectively). Conclusion: Eyes with pseudoexfoliation syndrome may be predisposed to an increased aqueous flare and macular edema after cataract surgery. This study outlines the need to determine the optimal anti-inflammatory medication after cataract surgery in patients with pseudoexfoliation syndrome.
  • Hariri, Amir H.; Velaga, Swetha B.; Girach, Aniz; Ip, Michael S.; Le, Phuc V.; Lam, Byron L.; Fischer, M. Dominik; Sankila, Eeva-Marja; Pennesi, Mark E.; Holz, Frank G.; Maclaren, Robert E.; Birch, David G.; Hoyng, Carel B.; Macdonald, Ian M.; Black, Graeme C.; Tsang, Stephen H.; Bressler, Neil M.; Larsen, Michael; Gorin, Michael B.; Webster, Andrew R.; Sadda, Srinivas R.; Nat Hist Progression Choroideremia (2017)
    PURPOSE: To identify valid and reproducible methods for quantifying anatomic outcome measures for eyes with choroideremia (CHM) in clinical trials. DESIGN: Reliability analysis study. METHODS: In this multicenter study, patients with confirmed genetic diagnosis of CHM were enrolled. All cases underwent spectral-domain optical coherence tomography (SDOCT) and fundus autofluorescence (FAF) imaging. Two graders independently delineated boundaries of preserved autofluorescence (PAF) and pre-served ellipsoid zone (EZ) on FAF and OCT images, respectively. The results of the 2 independent gradings of both FAF and OCT images were compared to assess the reproducibility of the grading methods. RESULTS: A total of 148 eyes from 75 cases were included. In 21% of eyes PAF and in 43% of eyes preserved EZ had extended beyond the image capture area. After exclusion of these eyes and low-quality images, 114 FAF and 77 OCT images were graded. The mean PAF areas from 2 independent gradings were 3.720 +/- 3.340 mm(2) and 3.692 +/- 3.253 mm2, respectively. Intraclass correlation coefficient (ICC) for these gradings was 0.996. The mean preserved EZ areas from 2 independent gradings were 2.746 +/- 2.319 mm2 and 2.858 2.446 mm2, respectively. ICC for these gradings was 0.991. CONCLUSIONS: Quantifying preserved retinal pigment epithelium and EZ areas on FAF and OCT images, respectively, in CHM patients is highly reproducible. These variables would be potential anatomic outcome measures for CHM clinical trials and could be studied and tracked longitudinally in choroideremia. (C) 2017 Elsevier Inc. All rights reserved.
  • Ylinen, Petteri; Laine, Ilkka; Lindholm, Juha-Matti; Tuuminen, Raimo (2017)
    Purpose: To specify the risk factors for pseudophakic cystoid macular edema (CME) in patients with diabetes. Setting: Kymenlaakso Central Hospital, Unit of Ophthalmology, Kotka, Finland. Design: Prospective case series. Methods: Patients with type 1 or type 2 diabetes having routine cataract surgery were evaluated. Spectral-domain optical coherence tomography imaging was performed before surgery and 1 month postoperatively. Results: The study comprised 93 patients (95 eyes). The central retinal thickness increase was 9.7 mu m 1.7 (SEM) in diabetic patients with no retinopathy, 22.7 +/- 8.6 mu m in those who had nonproliferative retinopathy, and 73.8 +/- 37.4 mu m in those who had proliferative retinopathy (P Conclusions: Young patient age and poor glycemic control were risk factors for postoperative central retinal thickness increase. This study showed it is necessary to identify, effectively treat, and followup with patients with diabetes who are at a greater risk for pseudophakic CME. (C) 2017 ASCRS and ESCRS
  • Sandler, Niklas; Kassamakov, Ivan; Ehlers, Henrik; Genina, Natalja; Ylitalo, Tuomo; Haeggstrom, Edward (2014)
  • Ala-Kauhaluoma, Marianne; Koskinen, Suvi M.; Silvennoinen, Heli; Vikatmaa, Pirkka; Nuotio, Krista; Ijäs, Petra; Relander, Kristiina; Lindsberg, Perttu J.; Soinne, Lauri; Summanen, Paula A. (2021)
    Purpose To compare subfoveal choroidal thickness (SFCT) and associated clinical variables in patients with carotid stenosis (CS) before and 6 months after carotid endarterectomy (CEA). Methods The prospective non-randomized Helsinki Carotid Endarterectomy Study - Brain and Eye Sub-sTudy included seventy patients (81% male, mean age 69 years) and 40 control subjects (77% male, 68 years), from March 2015 to December 2018. Ophthalmological examination included SFCT measured with enhanced-depth imaging-optical coherence tomography. Carotid stenosis (CS) was more severe (>= 70% stenosis in 92%) ipsilateral to the CEA than contralaterally ( Results At baseline, patients had thinner mean SFCT than control subjects in both eyes (ipsilateral, 222 versus 257 mu m and contralateral, 217 versus 258 mu m, p Conclusions Subfoveal choroidal thickness (SFCT) is thinner in patients with CS without association between SFCT and the grade of CS. Unchanged SFCT after CEA suggests, that choroidal vessels in severe CS are unable to react to increased blood flow. Bilaterally thin SFCT could be considered as yet another sign of CS.
  • Willcox, Mark D. P.; Argueso, Pablo; Georgiev, Georgi A.; Holopainen, Juha M.; Laurie, Gordon W.; Millar, Tom J.; Papas, Eric B.; Rolland, Jannick P.; Schmidt, Tannin A.; Stahl, Ulrike; Suarez, Tatiana; Subbaraman, Lakshman N.; Ucakhan, Omur O.; Jones, Lyndon (2017)
    The members of the Tear Film Subcommittee reviewed the role of the tear film in dry eye disease (DED). The Subcommittee reviewed biophysical and biochemical aspects of tears and how these change in DED. Clinically, DED is characterized by loss of tear volume, more rapid breakup of the tear film and increased evaporation of tears from the ocular surface. The tear film is composed of many substances including lipids, proteins, mucins and electrolytes. All of these contribute to the integrity of the tear film but exactly how they interact is still an area of active research. Tear film osmolarity increases in DED. Changes to other components such as proteins and mucins can be used as biomarkers for DED. The Subcommittee recommended areas for future research to advance our understanding of the tear film and how this changes with DED. The final report was written after review by all Subcommittee members and the entire TFOS DEWS II membership. (C) 2017 Elsevier Inc. All rights reserved.
  • Karjalainen, Pasi P.; Niemela, Matti; Laine, Mika; Airaksinen, Juhani K. E.; Ylitalo, Antti; Nammas, Wail (2017)
    Stent underexpansion is associated with worse outcome after stent implantation. Whether post-dilation (PD) improves outcome in patients with acute coronary syndrome (ACS) remains unclear. We performed post hoc analysis of outcome in patients from the BASE ACS (A prospective randomized comparison of titanium-nitride-oxide-coated bioactive stents with everolimus-eluting stents in acute coronary syndrome) trial who underwent PD versus those who did not. The BASE ACS trial randomized 827 patients (1:1) with ACS to receive either titanium-nitride-oxide coated bioactive stents or everolimus-eluting stents. The primary end point was major adverse cardiac events (MACE): a composite of cardiac death, nonfatal myocardial infarction (MI), or ischemia-driven target lesion revascularization. Follow-up was planned at 12 months and yearly thereafter for up to 7 years. Of 827 patients enrolled in the BASE ACS trial, 357 (43.2%) underwent PD. Median follow-up duration was 5 years. Patients who, underwent PD had less frequent nonfatal MI events at long-term follow-up, compared with those who did not (4.5% vs 8.5%, respectively, p = 0.02). The rates of MACE (15.7% vs 15.1%, respectively, p = 0.81), and the other endpoints, were not significantly different (p >0.5 for all). The results were consistent in propensity score matched analysis (270 pairs). In patients treated with bioactive stents, those who underwent PD had a trend for a fewer nonfatal MI events (p = 0.076). Comparably, in patients treated with everofimus-eluting stents, MACE and all the individual end points were comparable (p >0.5 for all). In conclusion, patients treated with early percutaneous coronary intervention for ACS who underwent PD had less frequent nonfatal MI events at long-term follow-up, compared with those who did not; MACE rates were not significantly different. (C) 2016 Elsevier Inc. All rights reserved.