PAPILLOPHLEBITIS: Illustrate Illustrate This Uncommon Syndrome

MEDICAL RETINA 32

RETINA TODAY A CLOSER LOOKCLOSER A PAPILLOPHLEBITIS: illustrate illustrate this uncommon syndrome. describe the cases of two patients with papillophlebitis to is the underlying mechanism in these cases. Below we sion of the central retinal vein and venous insufficiency, that inflammation of the optic disc, leading to compres BY ANDREAGROSSO,MD;JORGEI.CALZADA,JOHNRANDOLPH, and expeditepropertreatment. Basic awarenessofarareconditionmayhelpavoidunnecessarydiagnosticmeasures • • • •

JULY/AUGUST 2017 coagulopathies. reduce inflammationandtotreat anyunderlying and areoftencombinedwith anticoagulantsto Corticosteroids arethemainstay oftreatment macular edemaandpooracuity. papillophlebitis mayleadtoCRVOwithresulting If notdiagnosedandtreatedimmediately, neuritis orpapilledema. Papillophlebitis isoftenmisdiagnosedasoptic often inwomenbetweentheagesof20and35years. Papillophlebitis isarareconditionthatoccursmost AT A GLANCE It has been postulated younger than 50 years. in otherwise healthy adults orrhage and macular edema extent of intraretinal hem engorgement, and a variable hyperemia, retinal venous unilateral disc edema and characterized by painless disease. no history of vascular are present but there is vein occlusion (CRVO) features of central retinal tion in which the clinical Papillophlebitis is a condi 1 Papillophlebitis is 2-4

- - - lopathy characterized by either qualitative or quantitative C virus infection. GT is a rare, autosomal recessive coagu positive for Glanzmann thrombasthenia (GT) and hepatitis hematologic examinations were ordered and returned cally available at the time of initial diagnosis. Systemic and disc. Optical coherence tomography (OCT) was not clini in addition to leakage and late staining from the optic was significant for marked venous staining and leakage, four quadrants OS (Figure 2). Fluorescein angiography by diffuse superficial hemorrhages was observed in all OD, and more significant optic disc edema accompanied sure (IOP) was measured to be 16 mm Hg in each eye (OU). segment examination was unremarkable, and intraocular pres 20/20 in her right eye (OD) and 20/32 OS (Figure 1). Anterior history of trauma. Best corrected visual acuity (BCVA) was otherwise unremarkable, and the patient reported no recent in her left eye (OS). Medical history and ocular history were with a chief complaint of progressive, painless loss of vision Case No. 1 CASE REPORTS retinal hemorrhages (B). optic disc, retinal venous engorgement, and perivenous presentation of papillophlebitis OS, including edema of the swelling present OD (A). Red-free image showing typical Figure 1. Case No. 1: Moderate optic nerve disc On examination, moderate optic disc swelling was noted In October 2005, a 32-year-old white woman was evaluated A

and B ERICSIGLER,MD - -

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JULY/AUGUST 2017 Figure 3. Case No. 1: Ten years after initial diagnosis, OCT diagnosis, initial after years Ten 1: No. Case 3. Figure preservation with morphology foveal normal revealed scans layers. membrane limiting external and ellipsoid of and layer ellipsoid the of interruption perimacular However, layer nuclear outer the of level the at changes morphologic and exudation intraretinal previous indicating noted, were thickness layer fiber nerve peripapillary the Notably, edema. normal. remained has Figure 4. Case No. 1: Humphrey visual field (30-2 Swedish Swedish (30-2 field visual Humphrey 1: No. Case 4. Figure after years 10 standard) algorithm threshold interactive diagnosis. clinical - - - - - 3 com 3 β IIb α A diagnosis of papillophlebitis was made, and the patientthe and made, was papillophlebitis of diagnosis A Anterior segment examination was unremarkable, andunremarkable, was examination segment Anterior In 2006, a 24-year-old white woman was referred withreferred was woman white 24-year-old a 2006, In In June 2009, the patient was diagnosed with peritoneal with diagnosed was patient the 2009, June In After diagnosis, the patient was treated with systemic oralsystemic with treated was patient the diagnosis, After leakage and late staining from the optic disc. optic the from staining late and leakage Figure 2. Case No. 1: Fluorescein angiography is significant is angiography Fluorescein 1: No. Case 2. Figure to addition in leakage, and staining venous marked for

slow taper, and 100 mg aspirin. Her VA quickly returned toreturned quickly VA Her aspirin. mg 100 and taper, slow showed a subclinical pituitary microadenoma. pituitary subclinical a showed aby followed day, per prednisone oral mg 50 on started was a clinical pattern similar to CRVO. The patient underwentpatient The CRVO. to similar pattern clinical a test Further 6). and 5 (Figures evaluation retinal multimodal neuroimagingbut disorders, hematologic no revealed ing phate dehydrogenase deficiency and myocardial infarctionmyocardial and deficiency dehydrogenase phate OS. 20/20 and OD 20/25 was BCVA age. young a at revealedOD examination Fundus OU. Hg mm 14 was IOP painless vision loss OD. Her medical history was significantwas history medical Her OD. loss vision painless glucose-6-phos of history family a has she and smoking, for improved during follow-up (Figure 4). (Figure follow-up during improved 2 Case No. and edema. Bilateral visual field tests were also unremark also were tests field visual Bilateral edema. and thicknesslayer fiber nerve peripapillary the Notably, able. significantly abnormalities field Visual normal. remained has However, perimacular interruption of the ellipsoid layer andlayer ellipsoid the of interruption perimacular However, nuclearexternal the of level the at changes morphologic exudationintraretinal previous indicating noted, were layer nually, and her VA remained 20/20 with no recurrence ofrecurrence no with 20/20 remained VA her and nually, scans OCT diagnosis, initial after years Ten papillophlebitis. ofpreservation with morphology foveal normal revealed 3).(Figure layers membrane limiting external and ellipsoid affected eye, but it eventually improved to 20/20. to improved eventually it but eye, affected bian monitored be to her for arranged We mesothelioma. steroids 1 mg/kg/day, followed by a slow taper over severalover taper slow a by followed mg/kg/day, 1 steroids underlyingthe to due contraindicated was Aspirin weeks. thein months 6 for stable remained (VA) acuity Visual GT. plex, which result in bleeding tendencies that range from range that tendencies bleeding in result which plex, hemorrhage. life-threatening to purpura abnormalities of the membrane glycoprotein glycoprotein membrane the of abnormalities Images courtesy Torino Eye Hospital, Italy. Hospital, Eye Torino courtesy Images MEDICAL RETINA 34

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Images courtesy Torino Eye Hospital, Italy. as potential underlying risk factors. tive use, psoriasis, and pregnancy have also been postulated retinopathy, inflammatory bowel syndrome, oral contracep betes) or hematologic disorders. Dehydration, high altitude with systemic vascular disease (eg, arterial hypertension, dia affected most commonly. Papillophlebitis is often associated in women, with those between the ages of 20 and 35 years CRVO with resulting macular edema and poor VA. diagnosed and treated immediately, papillophlebitis may lead to acuity, unlike patients with traditional CRVO. However, if not papillophlebitis typically present with normal or near normal matic optic disc edema and venous engorgement, patients with retinal findings is an important and typical finding. Despite dra that a significant mismatch between VA at presentation and CLINICAL ASPECTS visual field and OCT in the affected eye 8 years later (Figure 7). follow-up, and the patient maintains 20/20 vision with normal 20/20. Visual field abnormalities significantly improved during leakage. late staining of the optic disc, marked venous staining, and Figure 6. Case No. 2: Fluorescein angiography showing hemorrhages of variable extent. hyperemia, retinal venous engorgement, and intraretinal angiography (B) revealing unilateral disc edema and Figure 5. Case No. 2: Red-free image (A) and fluorescein Historically, the prevalence of papillophlebitis is higher Historically, the prevalence of papillophlebitis is higher When a diagnosis of papillophlebitis is considered, remember A

JULY/AUGUST 2017 B - - - the central retinal vein typically seen in elderly patients. Due the central retinal vein typically seen in elderly patients. Due rhages that often resemble the atherosclerotic occlusion of retinal venous engorgement, and perivenous retinal hemor tracted monocular visual impairment, edema of the optic disc, initial clinical diagnosis (B, bottom). standard) at first presentation (B, top) and 7 years after visual field (30-2 Swedish interactive threshold algorithm engorgement at the level of the optic disc (A). Humphrey Figure 7. Case No. 2: Color fundus photo showing vein woman taking oral contraceptives. Figure 8. Retinal vein prethrombosis seen in a 20-year-old Clinically, papillophlebitis is characterized by mild but pro A B -

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RETINA TODAY

Image courtesy Royal Victorian Eye and Ear Hospital, Melbourne, Australia. and ischemia (Figure 10). tuosity of retinal arterioles to significant vascular congestion spectrum of microvascular abnormalities ranging from tor (Figure 9). The clinical course is variable. a “hot” disc without venous congestion or macular edema vascular risk factors. Clinically, fluorescein angiography shows sixth decades of life and is associated with traditional cardio encountered condition typically occurs during the fourth to tion of the medicine. contraceptives. Improvement is typically seen upon cessa limiting and is seen most often in young women taking oral amounts of macular edema and retinal ischemia. associated cardiovascular risk factors, and exhibits variable diverse set of vasculopathies, including those listed here: DIFFERENTIAL DIAGNOSIS over the disc reveal significant edema without traction. testing is crucial, as the macula is typically normal, and scans resolves once healed. shows enlargement of the blind spot, but this completely defect is typically absent. The visual field in the acute phase Neuroimaging is typically negative. Relative afferent pupillary does not disclose evidence of increased intracranial pressure. presentation and examination of the opposite ocular fundus indicate an optic nerve conduction defect and if the clinical noses are typically excluded if tests of visual function do not misdiagnosed as optic neuritis or papilledema. These diag to its occurrence in younger patients, papillophlebitis is often nonarteritic ischemic optic neuropathy. disc, generalized arteriolar narrowing consistent with Figure 9. Fluorescein angiography showing a “hot” optic Hypertensive retinopathy Nonarteritic ischemic optic neuropathy Retinal vein prethrombosis CRVO The differential diagnosis of papillophlebitis includes a

JULY/AUGUST 2017 . This condition typically occurs later in life, has . This condition typically occurs later in life, has 5,6 The diagnostic importance of OCT The diagnostic importance of OCT . This broad term applies to a . This broad term applies to a . This condition (Figure 8) is self- . This commonly . This commonly - - - - lying coagulopathies. Despite the fact that anticoagulant lying coagulopathies. Despite the fact that anticoagulant and/or aspirin to reduce inflammation and treat any under and are often coupled with anticoagulants such as heparin both systemic and periocular, are the mainstay of treatment inflammation at the optic nerve. Therefore, corticosteroids, venous insufficiency is presumed to be central retinal vein from traditional CRVO in that the underlying cause of THERAPY PATHOPHYSIOLOGY ANDRATIONALEFOR disease, Figure 11). infectious etiologies such as neuroretinitis. A diagnosis of cat scratch disease was made. Figure 11. Fluorescein angiography features are consistent with retinopathy. Figure 10. Color fundus photo showing severe hypertensive Papillophlebitis is a rare subtype of CRVO, but it differs Papillophlebitis is a rare subtype of CRVO, but it differs Bacillary angiomatosis 16 . This condition is associated with . This condition is associated with Bartonella henselae (cat scratch (cat scratch

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RETINA TODAY 1978;3(5):438-440. 4. EllenbergerCJr,MessnerK. Papillophlebitis:benignretinopathyresemblingpapilledema orpapillitis. 1992;12(1):3-11. 3. FongAC,SchatzH,McDonaldHR,etal.Centralretinalvein occlusioninyoungadults(papillophlebitis) 1966;45(10):62-68. 2. LonnLI,HoytWF.Papillophlebitis,acauseofprotracted benign opticdiscedema. June 26,2017. and veinocclusions.www.aao.org/bcscsnippetdetail.aspx?id=80edd3ee-356d-4ff9-bcec-d01c9bbbdf93. Accessed 1. AmericanAcademyofOphthalmology.BasicandClinical ScienceCourseexcerpt.Centralandbranchretinalartery dures for patients with typical clinical pictures. eliminate extensive and expensive neurodiagnostic proce phlebitis of the optic disc. Awareness of this syndrome can often overlooked cause of unilateral disc edema: presumed cases presented above focus on an underappreciated and the presence of ocular, orbital, or intracranial disease. The bulence (Reynolds principle) and endothelial inflammation. preexisting structural factors are more likely to develop tur culation is already damaged by hypertension. Patients with with patients with retinal vein occlusions, whose microcir lophlebitis have a healthy circulatory system in comparison distribution in the retinal network. global reflections of “optimality” and “efficiency” of blood eters (fractal dimension, tortuosity, and bifurcation) that are There is now the ability to assess a range of retinal param that conforms to Murray’s principle of minimum work. fact that the human circulatory system is a branching system MINIMUM WORK PROGNOSIS ANDMURRAY’S PRINCIPLEOF phlebitis and central retinal artery occlusion. following anti-VEGF injections in cases of combined papillo macular edema, and positive results have been reported vitreal steroids in cases of papillophlebitis with associated ischemia compared with steroid treatment alone. addition of anticoagulants either lessens or improves retinal papillophlebitis, our clinical experience has shown that the medications are not universally accepted in the treatment of The clinical picture of unilateral disc edema may suggest The benign natural course of papillophlebitis relies on the Reports in the literature have described the use of intra • rheumatologic referral. arthritis), youngwomenmaybenefitfromahematologic- underlying connectivetissuedisorder(eg,lupus,rheumatoid appropriate? retinal tractionin retinalvein occlusions inyoungpatients. Further, itismandatorytoscan theopticdisctoidentifyvitreo and toquantifyperipapillaryretinalnervefiberlayerthickness. OCT canbeusedtoshowthatthereisnomacularedema every 6monthsisthegoldstandard, butwhataboutOCT? papillophlebitis? LINGERING QUESTIONS

| Antiphospholipid antibodies and hyperhomocysteinemia; Antiphospholipid and hyperhomocysteinemia; antibodies Screening forhypercoagulablestatusmay includethefollowing: A: Q: Whenandfor whomisthrombophilia testing A: Q: What isappropriate follow-upforpatients with

JULY/AUGUST 2017 Obtaining visual fields and color fundus photography Obtaining visualfieldsandcolorfundusphotography Becausepapillophlebitiscanbethefirstsign ofan 12-16 10,11 Patients with papil Eye EarNoseThroatMon 3,7,8 n Ann Neurol Retina . 9 .

- . ------neurologist. unresponsive tosystemicsteroidsafterdiscussionwitha cerebral MRIneuroimagingfornational healthsystems? of atherosclerosis)andcounselingonuseoralcontraceptives. interpreted asaformofvenous thrombosisoracomplication strategies mayincludeaspirin(papillophlebitis be prevention offurtherthromboembolicepisodes.Preventive accordingly directthemanagement ofdiseaseand leadto of carriersmultipleprothromboticabnormalitiesmay preventive measures in high-risksituations.Identification involvement ofthefelloweyeandtoestablishappropriate • • edema. 7. ChangYC,WuWC.Intravitrealtriamcinoloneacetonideforthemanagementofpapillophlebitisandassociatedmacular 6. PurvinVA.Opticneuropathiesfortheneurologist. G20210A mutations. 5. CharakidasA,BrouzasD,AndriotiE,etal.PapillophlebitisassociatedwithcoexistingfactorVLeidenandprothrombin control study. 11. KawasakiR,CheAzeminMZ,KumarDK,etal.Fractaldimensionofretinalvasculatureandriskstroke:anestedcase 10. ShermanTF.Onconnectinglargevesselstosmall.ThemeaningofMurray’slaw. Natl AcadSciUSA 9. MurrayCD.Thephysiologicalprincipleofmimimumwork:I.vascularsystemandthecostbloodvolume. central retinalarteryocclusion. 8. LimaVC,PrataTS,LandaG,etal.Intravitrealtriamcinoloneandbevacizumabtherapyforcombinedpapillophlebitis diabetes 16. GrossoA,CheungN,VeglioF,WongTY.Similaritiesanddifferencesinearlyretinalphenotypeshypertension systems. 15. BombeliT,BasicA,FehrJ.Prevalenceofhereditarythrombophiliainpatientswiththrombosisdifferentvenous atherosclerosis? Ameta-analysisofthrombophilicfactors. 14. JanssenMC,denHeijerM,CruysbergJR,etal.Retinalveinocclusion:aformofvenousthrombosisorcomplication erythematosus andantiphospholipidsyndrome. 13. DurukanAH,AkarY,BayraktarMZ,etal.Combinedretinalarteryandveinocclusioninapatientwithsystemiclupus with retinalveinocclusionandunder60yearsofage. 12. ArsèneS,DelahousseB,ReginaLeLezML,PisellaPJ,GruelY.IncreasedprevalenceoffactorVLeideninpatients A: Q: What isthe appropriateness andsustainability of These testscanhelptopredicttheriskofrecurrencesor Additional thrombotic pregnancy. risk such factors as Factor VLeiden and prothrombin and G20210A mutations; n n n Eric Sigler, MD n n n John Randolph, MD n n n Andrea Grosso, MD n n n Jorge I. Calzada, MD An MRI should be considered for patients who are AnMRIshouldbeconsidered forpatients whoare Int Ophthalmol. Division ofRetinaandVitreous,Rockville Centre,N.Y. Haven, Fla. Mauro, Italy Monferrato, Italy,andatCentreforMacularResearchinSan AbbVie inMemphis,Tenn. Tennessee HamiltonEyeInstitute,both [email protected] financial disclosure:noneacknowledged ofLongIsland, retina specialistatOphthalmicConsultants [email protected] financial disclosure:noneacknowledged retina specialistatCenterforRetinaandMacular Disease,Winter [email protected] financial disclosure:noneacknowledged consultant, retinaspecialistatSantoSpiritoHospitalinCasale [email protected] financial disclosure:Alcon,Novartis,Genentech,Regeneron, president, CharlesRetinaInstitute;professor,Universityof J Hypertens. Am JHematol Neurology . 1926;12(3):207-214. 2011;29:1667–1675 Retina . 2002;70(2):126-132. 2008;28(4):291-296. . 2011;76(20):1766-1777. . 2002;22(2):239-240. Retin CasesBriefRep Can JOphthalmol . 2010;4(2):125-128. Semin Neurol Thromb Haemost Thromb Haemost . 2005;40(1):87-89. . 2000;20(1):97-110. . 2005;94(1):101-106 . 2005;93(6):1021-1026. JGenPhysiol . 1981;78(4):431-453. Proc