EPIPHORA: A STRATEGY FOR SOLVING THE Maple Grove Fridley Maplewood COMMON COMPLAINT JORDAN KEITH, OD, FAAO MINNEAPOLIS, MN Greg Kraupa, OD Steve Nauman, OD Mitch Albers, OD Brad Richter, OD Tina McCarty, OD Ashley Herde, OD Jordan Keith, OD OBJECTIVES • RECALL NORMAL ANATOMY OF TEAR PRODUCTION AND DRAINAGE • IDENTIFY CAUSES OF OVERPRODUCTION OF TEARS • IDENTIFY CAUSES OF REDUCED DRAINAGE OF TEARS • LIST TREATMENT OPTIONS TO PREVENT EPIPHORA Meibomian glands NASOLACRIMAL DRAINAGE SYSTEM Lipid Zeiss/Moll Reflex MLG Aqueous Emotional ALG Maintenance Mucin Goblet cells Cornea 1 Dry Eye Overproduction Exposure “Dry eye is a multifactorial disease of the Conjunctivochalasis tears and ocular surface that results in Epiphora symptoms of discomfort, visual disturbance, Eyelids and tear film instability with potential damage to the ocular surface. It is Punctual stenosis Poor drainage accompanied by increased osmolarity of the Canaliculitis tear film and inflammation of the ocular surface.” Dacryocystitis Lemp MA. The Definition and Classification of Dry Eye Disease. DEWS. The Ocular Surface. 2007; 5(2) NLDO TEARLAB CAUSATIVE MECHANISMS TEAR HYPEROSMOLARITY TEAR FILM INSTABILITY • RESULTS IN AN • CAN ARISE SECONDARY TO INFLAMMATORY CASCADE TEAR HYPEROSMOLARITY THAT DAMAGES THE OUTER OR CAN BE THE INITIATING SURFACE AND RELEASES EVENT IN THE DISEASE INFLAMMATORY MEDIATORS PROCESS INTO THE TEARS Lemp MA. The Definition and Classification of Dry Eye Disease. DEWS. The Ocular Surface. 2007; 5(2) Primary Sjogrens Secondary NAFL STAINING Aqueous Tear Primary lacrimal Deficiency (ADDE) gland deficiency • TBUT • LACRIMAL LAKE Secondary lacrimal gland deficiency • CORNEA DISEASE Dry Eye Non-Sjogrens Obstruction of • SEVERITY lacrimal gland ducts • JONES 1 Intrinsic Reflex Evaporative (EDE) hyposecretion Extrinsic Lemp MA. The Definition and Classification of Dry Eye Disease. DEWS. The Ocular Surface. 2007; 5(2) 2 LISSAMINE SJOGREN’S SYNDROME NEW GREEN DIAGNOSTIC CRITERIA (2 OF 3) STAINING Positive serum anti-SSA and/or anti-SSB OR [positive RF • SEVERITY AND ANA ≥ 1:320] Ocular staining score (OSS) ≥ 3 Presence of focal lymphocytic sialadenitis with focus score ≥ 1 focus/4 mm2 in a labial salivary gland biopsy Shiboski SC et al. American College of Rheumatology Classification Criteria for Sjögren’s Syndrome: SICCA Cohort. Arthritis Care Res (Hoboken). 2012 April ; 64(4): 475–487 LISSAMINE GREEN STAINING 1 2 3 Whitcher JP et al. Figure 2. Am J Ophthalmol. 2010 March ; 149(3): 405–415 Whitcher JP et al. Am J Ophthalmol. 2010 March ; 149(3): 405–415 FLUORESCEIN STAINING CONSECUTIVE PATIENTS WITH “PRIMARY” SS (N=163) 98% history of dry eye for average 10.4 years 25% extraglandular ocular manifestations 1 3 5 13% vision-threatening findings 42% extraglandular systemic manifestations Akpek EK et al. Ocular and systemic morbidity in a longitudinal cohort of Sjögren's syndrome. Whitcher JP et al. Am J Ophthalmol. 2010 March ; 149(3): 405–415 Ophthalmology. 2015 Jan;122(1):56-61 3 ® Observational Study Medicine OPEN Predicting the risk for lymphoma development in Sjogren syndrome An easy tool for clinical use Sjogern’s Syndrome has been shown to be an Sofia Fragkioudaki (MD)a, Clio P. Mavragani (MD)a,b,c,∗, Haralampos M. Moutsopoulos (MD, FACP, FRCP, independent risk factor for the development of MACR)b,c Abstract The heightened risk of non-Hodgkin lymphoma (NHL) development in primary Sjogren syndrome (SS) is well established. Several adverse clinical and laboratoryPatients predictors presenting have been described. with In theindependent current work, we aimed risk to formulate factors a predictive score for NHL non-Hodgkin’s lymphoma (NHL) development, based on clinical, serological, and histopathological findings at the time of SS diagnosis. In the present case–control study of 381 primary SSidentified patients and 92 and primary their SS patients risk with of concomitant NHL NHL,development: clinical, serological, and histopathological variables at the time of SS diagnosis were retrospectively recorded. For the identification of predictors for NHL development univariate• 2 andrisk multivariate factors models had were constructed.a 3.8% Salivary probability gland enlargement (SGE), lymphadenopathy, Raynaud phenomenon, anti-Ro/SSA or/and anti-La/SSB autoantibodies, rheumatoid factor (RF) positivity, monoclonal gammopathy, and C4 hypocomplementemia• 3 to 6 risk were factors shown to had be independent a 39.9% predictors probability for NHL development. (OR On (95%CI): the basis of the 16.6 number of Afflicting about 5% independent risk factors identified, a predictive risk score for NHL development was formulated. Thus, patients presenting with 2 risk factors[6.5 had– a42.5], 3.8% probability P < of NHL0.05 development,) those with 3 to 6 risk factors 39.9% (OR (95%CI): 16.6 [6.5–42.5], P<0.05), while in the presence of all 7 risk factors the corresponding probability reached 100% (OR [95%CI]: 210.0 [10.0–4412.9], P < 0.0001).• All In conclusion,7 risk anfactors easy to use the diagnostic corresponding scoring tool for NHL development probability in the context reached of SS is presented. 100% This model is Estimated to be 7-19 fold higher risk compared to general highly significant for the design of early therapeutic interventions in high risk SS patients for NHL development. Abbreviations:(OR [95%CI]:MALT = mucosa 210.0 associated [10.0 lymphoid– tissue,4412.9], MSG = minor P< salivary 0.0001 gland, NHL = non-Hodgkin lymphoma, PNS = population peripheral nervous system, RF = rheumatoid factor, SGE = salivary gland enlargement, SS = Sjogren syndrome. Keywords: adverse predictors,Fragkioudaki non-Hodgkin lymphoma, et al. Sjogren Medicine. syndrome 2016 95:25 1. Introduction Although mucosa associated lymphoid tissue (MALT) mainly in the salivary glands is the prominent histological lymphoma Sjogren syndrome (SS) is a common systemic autoimmune disease type with a 1000-fold increased risk[4] among primary SS usually confined in the exocrine glands (mainly salivary and Fragkioudaki et al. Medicine. 2016 95:25 patients,[2,10] more aggressive subtypes including diffuse large lachrymal), leading to desiccation of oral and ocular mucosal B-cell lymphomas can also occur.[2,11] tissues. Nevertheless, systemic manifestations can arise in a Lymphomagenesis in the setting of autoimmunity and proportion of SS individuals[1] and B-cell non-Hodgkin lympho- particularly of SS is considered a multifactorial process, not ma (NHL) development represents a severe complication, entirely elucidated yet. Genetic aberrations, including chromo- afflicting approximately 5% of patients.[2] The risk of NHL somal translocations,[12] mutations of the tumor suppressor gene occurrence in the setting of SS, the highest among systemic p53,[13] and polymorphisms of molecules with regulatory role in autoimmune diseases,[3,4] has been previously estimated to be both innate and adaptive immune activation pathways[14,15] have 7- to 19-fold higher compared to the general population.[3–9] been so far implicated. Moreover, according to previous studies, clinical features at disease presentation, such as persistent salivary Editor: Qinhong Zhang. gland enlargement (SGE)[16] and palpable purpura,[16,17] labora- SF and CPM contributed equally to this work. tory abnormalities, like lymphopenia, monoclonal type II The authors have no funding and conflicts of interest to disclose. cryoglobulinemia, and hypocomplementemia[16–18] as well as Supplemental Digital Content is available for this article. intense lymphocytic infiltrations[19] and germinal center forma- [20] a Department of Physiology, b Department of Pathophysiology, c Joint Academic tion in minor salivary gland (MSG) biopsies, have been Rheumatology Program, School of Medicine, National and Kapodistrian identified as adverse predictors for SS-related NHL development. University of Athens, Athens, Greece. As a result, at their first evaluation, SS patients can be classified ∗ Correspondence: Clio P. Mavragani, Department of Physiology, School of into separate subsets with distinct likelihood for lymphoma Medicine, National and Kapodistrian University of Athens, M. Asias 75, 11527 development. Athens, Greece (e-mail: [email protected]). The current study aimed to create a predictive tool in Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. This is an open access article distributed under the Creative Commons clinical practice for SS-related NHL development, based Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and on clinical, hematological, serological, and histopathological reproduction in any medium, provided the original work is properly cited. features, observed early at disease diagnosis. Prompt diagnosis Medicine (2016) 95:25(e3766) would allow early therapeutic intervention with the ultimate Received: 8 December 2015 / Received in final form: 25 April 2016 / Accepted: goal to decelerate the progression of benign to malignant 29 April 2016 lymphoproliferation. http://dx.doi.org/10.1097/MD.0000000000003766 1 35% EDE Dry 30% 10% Neither Eye ADDE Disease DRY EYE TREATMENT 25% EDE & ADDE Lemp MA. Cornea. 2012 May;31(5):472-8 OBESE MALE/RED WATERING EYES EVERY FLOPPY EYELID SYNDROME MORNING • MOST COMMON IN OBESE MALES WITH SLEEP APNEA • 5.7% (N=12/209) PATIENTS WITH SLEEP APNEA HAVE NTG Lin PW et al. J Glaucoma. 2011; 20(9): 553-8 4 LACRIMAL LAKE DISRUPTION CONJUNCTIVOCHALASIS • OFTEN OVERLOOKED • TWO MECHANISMS FOR CAUSING EPIPHORA 1) MORE COMMON: INTERFERENCE BY THE REDUNDANT CONJUNCTIVA WITH