Posterior(Segment(Grand(Rounds( from(the(Bluff(City(11/28/18 1...
Transcript of Posterior(Segment(Grand(Rounds( from(the(Bluff(City(11/28/18 1...
11/28/18
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Posterior(Segment(Grand(Rounds(from(the(Bluff(City(
Andrew+Rixon+OD,+FAAO59713-PS
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•No+Financial+Disclosures
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Case+CB
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CB• 44+yo WF+c/o+ reduced+ vision+ OS• Slowly+ worsening+ over+ past+8E10+months• CL+examination+ at+outside+ doc+had+VA+ reduced+ to+20/40• Previously+ correctable+ to+20/20• 1+wk ago+covered+up+ OD+and+ couldn’t+ see+cars+ in+ front+of+her+ through+ OS+but+could+ see+ trees+ around+ it
• Tinnitus+ has+worsened+ recently• Hx of+Migraines,+ no+ worsening+ of+ these• Meds:+ Loratidine 10+mg qday, methocarbamol 500+mg qhs prn,+naproxen 250+mg+bid,+ and+promethazine+ 25+mg+q6hours prn.
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CB(Ocular(findings/Ocular(Hx
• BCVA:+20/20+OD,+20/150+OS• Pupils:+1++APD+OS• Amsler:+normal+OD,++metamorphopsia of+entire+grid+OS• Color+vision:+Unremarkable• Oc Hx:+ONH+drusen OU+c+RNFL+thinning+and+VF+defect• Previous+Photos/OCTs/VF+to+follow….• OCTs+unchanged+at+that+visit• VF+from+this+visit+attached
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Disc(Photos
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RNFL(OU
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GCL(OU
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XCSectional(Scans
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Historical((VFs
1 0
VF(on(day(of(Exam
1 1
Grayscale(Comp(1yr(prior➡ ️ Day(of(Visit(OS
VFI+71%+ VFI+51%12
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Is(the(VA(loss(due(to(the(drusen???
J Glaucoma .2009;18(5):373–378 1 3
Unlikely……..
1 4
MRI(c(Contrast(
1 5
Different(MRI(techniques
T1+weighted T2+weighted T1+with+contrastSlide+ Courtesy+ of+ Jess ica+Haynes + OD,+ FAAO 16
Dx…….Planum Sphenoidale(Meningioma• Tx:+Elective+Right+Orbitofrontal+craniotomy+resection+of+planummeningioma“Once+the+tumor+was+identified,+we+looked+along+the+ipsilateral+side+until+
the+ipsilateral+optic+nerve+and+carotid+artery+were+idenitifed.+The+tumor+was+carefully+dissected+off+these.+We+then+worked+across+the+planum.+We+identified+a+significant+number+of+feeders+to+the+tumor.+These+were+carefully+coagulated+and+cut.+We+continued+to+work+across+to+the+other+side,+attempting+to+identify+the+contralateral+optic+nerve.+This+was+somewhat+challenging+as+the+optic+nerve+was+found+to+be+completely+surrounded+by+tumor+and+in+fact+the+tumor+was+invested+into+the+optic+canal.+We+proceeded+to+dissect+the+tumor+out+of+the+optic+canal.+We+also+opened+the+falciformligament+around+the+ipsilateral+side+in+order+to+release+the+optic+nerve+which+was+pinned+laterally+by+the+tumor”
https://vimeo.com/17662043717
Planum Sphenoidale(Meningioma• Account+for+5E10%+of+all+intracranial+meningiomas• Constitute+2%+of+all+primary+intraEcranial+tumors• F>M+predilection• Benign+and+typically+slowEgrowing+tumors• Most+patients+remain+asymptomatic+until+tumor+reaches+>4cm• ~2/3+of+pts+have+monocular+reduced+vision+as+1st symptoms++
Can Fam Phys ician 2017;63:288-9, 291 BMJ$ Case$Reports $ 2011;+ doi:10.1136/bcr.07.2011.45 11+https :/ / radiopaedia.org/cases/plan um Esphe noi daleE me ningio ma E9Romanian Neurosurgery (2013)+ XX+ 1:+ 92+E 99 h ttp s://neup sykey.com/su r gic al E man ag em en tE
o fEmid l in eEan terio rEsku l l Eb aseEm en in giom as /1 8
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Pre(and(post(tumor(removal
Slide+ Courtesy+ of+ Jess ica+Haynes + OD,+ FAAO19
VF(Pre(and(Post(Tumor(Removal
2 0
OMIC(Claims(2008C2014
• Oncology(claims. There+were+27+claims.+Failure+to+diagnose+melanoma+resulted+in+six+claims+and+two+payments.+Pituitary+tumors+were+allegedly+missed+in+four+claims+but+no+payments+were+made.+A+delay+in+diagnosing+glioma+led+to+three+claims+and+two+payments,+including+a+settlement+of+$2,000,000,+the+largest+ one+in+the+study.+There+were+three+lacrimal+cancer+claims+with+one+payment,+three+optic+nerve+tumors+with+no+payments,+and+one+trigeminal+schwannoma+claim,+which+settled+for+$1,000,000.
https :/ /www.omic.com/diagnosticEe rr or Ety pesEan dEca uses/ 2 1
Optic(Disc(Drusen Diagnostics
• CT• FAF• Ultrasound• OCTEEDI
Retina 2008% Jan)28(1):143 06 .2 2
CT
Turk+ J+Ophthalmol 46;+ 5:+201623
FAF
2 4
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B(Scan
2 5
SDCOCT(XCsections((Black(on(white
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Ophthalmology 2017)124:66 07 3
EDI(of(ONH(DrusenC3(categories
2 7
J+Neuro+ Ophthalmol2018;38:299–307
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John son L,+et+al . + Arch $Oph th a lmo l .$2 0 0 9 ;1 2 7 (1 ):4 5 E4 9 .+
Si lverman A,+et+al . + J$Neu ro $ Oph th a lmo l 2 0 1 4 ;3 4 :+1 9 8 E2 0 5 .
Slo tn ick,+ S, +OVS. $ 2 0 1 2 ;8 9 (5 ):+1 E5 .
Evolution(of(Imaging
Slide+ courtesy+ of+ Catherine+ Hogan+ OD,+ FAAO 29
Pros/Cons(of(Drusen Diagnostics
Silverman+ et+ al:+J$ Neuro;Ophthalmol 2014;+ 34:+ 198E20530
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The(RNFL(problem
Graefes Arch$ Clin Exp Ophthalmol (2014)+ 252:1653–166031
Pseudo(vs(True(EdemaOLD
VS
Arch$ Ophthalmol.+ 2009;127(1):45E49
NEW
Asia-Pac J Ophthalmology 2018;7:271–279 3 2
Serial(OCT(in(Neuro….
Thanks + to+ Jeremy+ W.+Anderson+ OD,+ FAAO 33
DR.B+Case
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Dr.B
• 45+yo AM+cc:+visual+disturbanceF:+constantO:+suddenL:+OS,+superior+central+fieldD:+24+hrsA:+(E)fortification+scotoma,+(E)HA,+
(E)flashes,R:+None
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Dr.B
• BCVA:+OD:+20/20+OS:+20/20E D+and+N• PERRL+(E)APD• FROM+OU• CF:+Full+OD,+OS+distortion+of+face+on+FA• TAG;+ 17+mmHg+OD,OS• BP:+118/84mmHg+RAS• SLEx:+Unremarkable• PostPole:+as+follows
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Dr.B
• SysHx:+kidney+stone+sx 1986,+last+med+exam+6+mo+c+comprehensive+blood+work+(E)sleep+apnea• OcHx:+Glaucoma+according+to+retinal+specialist+friend+in+Iran• Meds:+Finasteride 1mg+qd po• Allergies:+Iodine,+(E)anaphylaxis
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Dr.B
Image+ credit:+ Andrew+ Rixon+ OD,+ FAAO+ 3 8
Phases/Fill( times(of(IVFA
Phases
• Prearterial• Arterial• Arteriovenous• Venous• Recirculation
Fill(times
• InjectionE0+sec• Prearterial/ChoroidalE9E12+sec• ArterialE10E13+sec• ArteriovenousE12E15+sec• VenousE13E17+sec• RecirculationE5+min
Cavallerano,+ Gutner,+ Oshinskie L+Macular$ Disorders 3 9
PreCarterial
Cavallerano A,+Gutner+R,+ Oshinskie L .Macular$Disorders .$ p$48$ Image+ Credit:+ Andrew+ Rixon+ OD,+ FAAO 40
Arterial(Characteristics
• Central+retinal+artery+ begins+to+fill• Subsequent+display+of+all+retinal+arterioles• This+is+phase+at+which+arm+to+retina+time+is+calculated• Mean+ART+is+11.2± 3.3+seconds
Image+ Credit:+ Andrew+ Rixon+ OD,+ FAAO41
Arteriovenous Characteristics
• Retinal+venules and+veins+begin+to+fill• Laminar+flow+in+veins• Definition+to+capillaries
Image+ +Credit:+ Andrew+ Rixon+ OD,+ FAAO 42
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Arterial/Arteriovenous
Cavallerano,+Gutner,+Oshinskie L+Macular$DisordersImage+ Credit:+ Andrew+ Rixon+ OD,+ FAAO Photo+ Credit:+ Andrew+ Rixon+ OD,+FAAO43
Venous
• Venous+filling+is+now+complete• Intensity+fades+in+the+choroid+and+arterioles
Image+ Credit:+ Andrew+ Rixon+ OD,+ FAAO 44
Venous/Recirculation
8(minutes
Image+ Credit:+ Andrew+ Rixon+ OD,+ FAAO 45
Recirculation 8+minutes
• Mild+residual+staining+of+choroid,+sclera,+and+optic+nerve
Image+ Credit:+ Andrew+ Rixon+ OD,+ FAAO 46
IVFA
Image+ credit:+ Andrew+ Rixon+ OD,+ FAAO+
40+Seconds! 57+Seconds!
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Dr.BCDx and(Managment• HRVO+OS,+nonischemic• Start+ 81mg+ASA+qd p.o• Comprehensive+bloodwork;
CBC+c+Diff,+Hb1AC,+ANA,+PT,PTT,+Protein+S+and+C,+antithrombin,+FTAEABS,+RPR,+Homocysteine,+lipid+profile,+antiphospholipid+antibodies+• EKG,+carotid+ultrasound• Could+also+have+orderedEprotein+electrophoresis,+factor+V+leiden• RTC+3+weeks+repeat+IVFA+(2’+to+pt+leaving+country)
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HRVO(review
• 5E13%+ of+VOs
• Presumed+ CRV+ does+ not+ become+a+single+entity+ until+ it’s+ posterior+ to+ lamina
• Leaves+ individual+ branches+ more+susceptible+to+ impingement+ at+lamina
• Highest+ age+ incidence+ 65E74yoa• Cardiovascular+ Dz,+ Htn,+ DM,+hyperlipidemia
• Less+ then+ 10%+ occur+under+ age+45• Should+ consider+ thrombophilia+ in+under+ 50
Hay reh SS.% Retina l %v e in %oc c lus ion.%Ind ian%J %Ophthalmol 1994)42:109032Hayreh SS.+Prog Retin Eye$Res .+2005;24:+493–519+Lahey JM,+Tunc M,+Kearney+J,+et+al.+Ophthalmology.$2002;109:126‒131.+ 4 9
Coagulation(Cascade
https :/ /www.researchgate.net/ publica tio n/2369 212 66_U tilizatio n_o f_C oagul atio n_ Assays_in_Cli nical_T hera peu tics
Browning+DJ.+ Retinal+Vein+Occlus ions :Evidence Based+Management+ 2012+ISBN:978E1E4614E3438E2
5 0
Results
• All+testing+normal,+exception+total+protein+S• Protein+S+works+to+inhibit+excessive+clotting• Pts+levels+were+low,+may+have+resulted+in+thromboembolic event• Bloodwork repeated,+total+protein+S+normal
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Was(I(Zebra(Hunting?
Browning+DJ.+ Retinal+Vein+Occlus ions :Evidence Based+Management+ 2012+ISBN:978E1E4614E3438E2 5 2
Results• Repeat+ IVFA+showed+no+filling+defect• No+neo+on+gonio*• Pt+had+self+d/c+81mg+ASA• Had+decided+not+consult+c+hematology• RTC+4E6mo+DFE• Pt+educated+no+Glaucoma
Image+ credit:+ Andrew+ Rixon+ OD,+ FAAO+
5 3
Why(Gonio???
Alexander+ L,+ Primary+ Care+ of+ the+ Posterior+ Segment+5 4
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Was(ASA(impactful?
• 686+ischemic+and+nonEischemic+CRVO+and+nonEischemic+HRVO• All+types+ showed+more+ severe+ hemorrhaging+ in+anticoagulation+group• Initial+VA+and+VF+were+ worse+ in+anticoagulation+ group+ in+nonEischemics• Higher+ visual+acuity+ deterioration+ in+anticoagulation+ group• There+ was+ NO+benefit+ to+existing+ therapy+ or+initiation+of+therapy
Hayreh SS,$et$ al.$ Ophthalmology$ 2011;118:1603–1611$ 5 5
Pathophysiology(of(RVO/Virchow’s(Triad
• Abnormalities+of+the+vessel+wall+• Alterations+in+the+blood+i.e.+
EAbnormalties of+viscosity+and+coagulation
• Alterations+in+blood+flow.+
Hayreh SS.+Prog Retin Eye+ Res +24+ (2005)+ 493–519+Browning+DJ.+ Retinal+Vein+Occlus ions :Evidence Based+Management+ 2012+ISBN:978E1E4614E3438E2 5 6
HypofluorescenceCase
Image+ Credit:+Andrew+ Rixon+ OD,+ FAAO
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Image+ Credit:+Andrew+ Rixon+ OD,+ FAAO
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XCSection(through(ONH
Image+ Credit:+ Andrew+ Rixon+ OD,+ FAAO 59
34(seconds(p(injection
Image+ Credit:+Andrew+ Rixon+ OD,+ FAAO
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3(min(p(injection
Image+ Credit:+Andrew+ Rixon+ OD,+ FAAO
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Are(you(on(Warfarin?
• 84yo+WM• Loss+of+vision+OD+x+1week• Painless• LP+vision• “I+sneezed+and+heard+a+pop+in+my+ear+and+then+woke+up+and+couldn’t+see”• Hx of+Htn,+Hld,+CAD,+CHF,+A+Fib• Last+INR+5.1
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B(ScanPosterior+ Hyaloid+ Face
RetinaChoroid
SuprachoroidalHeme
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Treatment(Case….
• 67yo+AAM+ cc:+comprehensive+ eye+exam• 2’+cc:+Blur+ and+ haze+OS+x+3E4mo+ ++ ++ ++ ++ +• (E)+flashes/floates ,+ (E)LOV+ ++ ++• Oc Hx:+DED,+NS+cataracts+ (E)surgery+ (E)+Trauma+ + (E)+family+ Hx• Hx of+ reduced+ VA+ OU+without+ organic+ ocular+ etiology,+ past+OCT+ unremarkable+ +and+VF+ ureliable
• Sys+Hx:++(+)+Htn (+)Gout• SysMeds:+ +Amlodipine,+ Atenolol,+ Albuterol,+ Colchicine,+ Enalapril,+ Furosemide,+and+ ibuprofen.+
• NKDA• Social+ Hx:+Unremarkable+ ++
6 4
Fundus(OS
Image+ Credit:+ Andrew+ Rixon+ OD,+ FAAO 65
Representative(XCsections
Image+ Credit:+ Andrew+ Rixon+ OD,+ FAAO
66
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IVFAs
Image+ Credit:+ Andrew+ Rixon+ OD,+ FAAO,+ Jim+ Williamson+ OD,+ FAAO,+ Michael+ White+ OD 67
45(and(70(sec
Image+ Credit:+ Andrew+ Rixon+ OD,+ FAAO,+ Jim+ Williamson+ OD,+ FAAO,+ Michael+ White+ OD68
Later…..
Image+ Credit:+ Andrew+ Rixon+ OD,+ FAAOJim+ Williamson+ OD,+ FAAOMichael+ White+ OD 69
VEGF(Levels(in(Retinal(Vascular(Disorders
Aiello+ LP,+ et+ al.+N$Engl J$ Med.1994;331:480–148 7 70
BRAVO/RETAIN/BRIGHTER• BRAVO
EExplored+ use+of+monthly+ injections+ of+ ranibizumab for+BRVOEassociated+ CME+ over+6mo+vs+ shamE6mo+resultsE61%+ of+0.5mg+gained+ >3+VA+ lines+ vs+29%+ in+ sham+RETAINEMean+ f/u+49mo+E50%+ had+edema+ resolution+ for+>6mo+ post+ last+ injectionELast+ injection+ within+ 2yrs+of+baseline+ in+ 76%E~80%+ had+ a+final+ BCVA+ of+20/40+ or+betterBRIGHTERERanibizumab vs+Ranibizumab/la ser+ vs+LaserEInjections+ for+3mo,+ then+ prnE24mo+ showed+ Ranibizumab alone+ sufficient,+ addition+ of+ laser+ did+not+ improve+ outcomesTadayon i R ,+et+ al . , +Oph th a lmo lo g y 2 0 1 7 ;1 2 4 :1 7 7 8 E1 7 87 ,+ +C ampoch iaro PA,+et+al . +Oph th a lmo lo g y. 2 0 1 4 ;1 2 :20 9 E1 9
Campoch iaro PA,+Oph th a lmo lo g y. +2 0 1 0 ;+1 1 7 (6 ):+1 1 0 2 –1 1 1 2.7 1
VIBRANT
• EIVTEAflibercept (IAI)+vs+Grid+ laser+ on+macular+ edema+2’+ to+BRVOEIAI+group;+ sham+ laser+ baseline,+ injection+ q4wks+ through+ 24wks,+ then+q8wks+ through+ 48EGrid+ group;+ baseline+ laser,+ sham+ injections+ q4wks+ through+ 24wks,+ rescue+IAI+after+ week+24+ if+needed
24+wk Results:E %+of+eyes+ improving+ >15+ letters+ was+ 52.7%+ in+ IAI,+26.7%+ in+ laserEReduction+ in+ central+ macular+ thickness+ was+ 280.5um+ vs+128.0um52+wk results+E Equivocal+ due+ to+ rescue+ IAI+after+24wksE8wk+ injection+ intervals+ post+ initial+ 24wks+ maintained+ VA+and+ mac+thickness
Clark+ WL,+et+ al.+Ophthalmology.+ 2016;123:+ 7 2
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GENEVACMean( BCVA(change(from(Baseline
Slide+ courtesy+ of+ Allergan73
Ozurdex
7 4
Good+or+Bad+Compensation???
75 Image+ credit:+ Andrew+ Rixon+ OD,+ FAAO+ and+ Michael+ White+ OD76
IVFA(OD20(sec 34(sec
Image+ credit:+ Andrew+ Rixon+ OD,+ FAAO+ and+ Michael+ White+ OD77 Image+ credit:+ Andrew+ Rixon+ OD,+ FAAO+ and+ Michael+ White+ OD
64+sec 120+sec
78
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IVFA(OS150+sec 150+sec
Image+ credit:+ Andrew+ Rixon+ OD,+ FAAO+ and+ Michael+ White+ OD79
OCTCA( Color(
Image+ credit:+ Andrew+ Rixon+ OD,+ FAAO+ and+ Michael+ White+ OD80
OCTCA( Superficial(vs(Deep
Image+ credit:+ Andrew+ Rixon+ OD,+ FAAO+ and+ Michael+ White+ OD 81
Collateral(vs(Neo(on(OCTCA
Sogawa K,% et% al.% Int Med2 Case2 Rep2 J.% 2015 Oct 23)8:26306.Image+ credit:+ Andrew+ Rixon+ OD,+ FAAO+ 8 2
Pachychoroid
https :/ /blog.goodaudience.co m/t heE eosEel eph ant EinE the Er oo mE3 5fb 9bd 1e94 83
Choroidal(Thickness1,3
• Affected+ by+a+multitude+of+factors
At(Birth Age(90 Subfoveal Thickness What( is(thick?
200+um 80+um 220+to 350+um >+390+um
Slide+Courtesy+Meagan+Williams+ OD,+FAAO84
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Factors(Affecting(Choroidal(Thickness2,4,5
• Age*• Choroidal+thickness+decreases+by+15+microns+per+decade+• 4+micron+decrease+per+year
• Axial+length• Decrease+ in+15+microns+for+every+1D+increase+in+myopic+refractive+error
• Gender• Thicker+in+men+by+18+%
Slide+Courtesy+Meagan+Williams+ OD,+FAAO 85
Factors(Affecting(Choroidal(Thickness2,4,5
Other+Factors
Sympathetic+Tone
Pregnancy
Metabolic+Disease
SmokingSystemic+
Inf lammatory+Disease
Tumors
Neurological+Disease
Slide+Courtesy+Meagan+Williams+ OD,+FAAO 86
Increased(Choroidal(Thickness
• Pachychoroid• >300+microns
• Characteristics• Increased+choroidal+thickening• Pathologically+dilated+veins+in+Haller’s+layer+(pachy veins)• Thinning+in+Sattler’s+layer+and+choriocapillaris
Akkaya S.++Spectrum+ of+pachychoroid+ disease.+ +Int Ophthalmol.$ 2017;+ 1E8
Slide+Courtesy+Meagan+Williams+ OD,+FAAO 87
Increased(Choroidal(Thickness
• Pachychoroid+“phenotype”
• Pachychoroid+vascular+changes+cause+focal+disruptions+in+RPE+and+Bruch’s+membrane
Choroidal+hyperpermeability
Dilated+choroidal+vessels
Focal+or+diffuse+choroidal+ thickness+increase
Akkaya S.++Spectrum+ of+pachychoroid+ disease.+ +Int Ophthalmol.$ 2017;+ 1E8
Slide+Courtesy+Meagan+Williams+ OD,+FAAO 88
Pachychoroid(Disease(Spectrum3
Pachychoroid+Pigment+Epitheliopathy(PPE) Central+Serous+
Chorioretinopathy (CSR)
Pachychoroid+Neovasculopathy
PolypoidalChoroidal+Vasculopathy (PCV)
Akkaya S.++Spectrum+ of+pachychoroid+ disease.+ +Int Ophthalmol.$ 2017;+ 1E8
Slide+Courtesy+Meagan+Williams+ OD,+FAAO 89
Pachychoroid(Pigment(Epitheliopathy6,7• “Form+fruste”+or+incomplete+version+of+CSR• No+SRF
• Pachychoroid+phenotype• Reduced+fundus+tessellation• Unilateral+or+bilateral• RPE+abnormalities• Small+RPE+detachments• Absence+of+SRF+and+drusen
• Commonly(confused(with(ARMD,(macular(dystrophies,(choroiditis
Slide+Courtesy+Meagan+Williams+ OD,+FAAO
Retina 2013;33:1659E1672Retina 2016;36(3);499E516
90
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Case(Example:(PPE
9 1
Case(Example:(PPE
439(um
9 2
JG(Case
9 3
JG(Case(details• 82yo+WM+for+Dr+directed+f/u+of+Dry+AMD,+unspecified+stage• Dx AMD+in+2008+in+our+clinic• Uses+AREDS2+x2yrs+(inconsistent+recommendations)• Sys+Hx:+DM+Type+II,+Htn,+Chronic+Ischemic+Heart+Disease,++• Smokes+rare+cigar,+ no+Hx of+cigarette+smoking• OcHx:+Amarosis fugax+5mo+previous,+CT,+CTA,+Carotid,+EKG+unremarkable,++1++NS+OU• (E)metamorphopsia
94
Color(Fundus(Photos
9 5
FAF
9 6
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XCsections(OD
9 7
XCsections(OS
9 8
AMD(vs(PachychoroidCAll(age(82yo(WMs
Intermediate+AMD Advanced+AMD
Our+Patient99
Choroidal(Thickness(and(AMD???• Proposal+that+choroidal+thinning+and+insufficiency+contributes+to+outer+retinal+ischemia• If+choroid+cannot+supply+oxygen+and+remove+waste+from+photoreceptors+and+RPE+it+may+contribute+to+AMD+worsening• Although+physiologic+aging+diminishes+choroidal+thickness,+further+decrease+ is+observed+in+dry+and+wet+AMD+independent+of+controls• RPD+associated+with+choroidal+thinning• Choroidal+thickness+change+associated+with+resultant+GA• Debate+ in+the+literature+continues…..
Graefe's Archive for Clinical and Experimental Ophthalmology (2018) 256:511–518Am J Ophthalmol. 2018;191:23-33 Surv Ophthalmol 2016; 61:+ 521–37Am$ J$ Ophthalmol 2015;159:617E626 10 0
CC(Case
1 0 1
CC:• 36+yo• Cc:+new+patient+presents+with+cc:+of+a+brown+spot+in+central+vision+OD+x+1wk
EReports+it+is+like+he+is+looking+through+a++“coffee+stain"+EReports+the+spot+is+located+in+his+central+vision+and+does+not+move;+EDenies+any+flashes,+floaters,+or+LOV+OU.+EDenies+any+associated+signs+and+symptoms
• Pertinent+Hx:+Recent+divorce,+PTSD,+works+in+engineering
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Fundus(Photos
Image+ credit:+ Andrew+ Rixon+ OD,+ FAAO103
November
Images + credit:+ Andrew+ Rixon+ OD,+ FAAO+ 1 0 4
CSCR(Type(I(and(II
Cavallerano,+ Gutner,+ Oshinskie Macular$ Disorders $ 199710 5
OS(is(great!
Images + credit:+ Andrew+ Rixon+ OD,+ FAAO 106
December=Elplerenone Time
Images + credit:+ Andrew+ Rixon+ OD,+ FAAO 107
CSCR(Review• Pathogenesis+multifactorial,+poorly+understood+• Characterized+by+serous+detachment+of+the+neurosensory+retina• Additionally;+focal+detachments+of+RPE,+angiographic+leakage+at+level+of+RPE,+choroidal+hyperpermeability,+pachychoroid• Associated+with+endogenous+hypercortisolism,+type+A+behavior+and+pregnancy,+administration+of+ACTH+or+exogenous+administration+of+corticosteroids• Most+resolve+spontaneously+with+minimal+sequelae• 30E45%+of+patients+have+recurrent+disease+and+a+poorer+visual+prognosis.+
Nicholson+ BP,+ et+al.+ Surv Ophthalmol 2018;63(1):1E8Daruich A,+ et+ al.+Prog Retin Eye$Res .+ 2015:48:82e118+
1 0 8
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Mineralcorticoid Pathway(Hypothesis• Endogenous+cortisol+metabolism+disturbances+have+also+been+associated+with+CSCR+• Suggests+glucocorticoids+paradoxically+favor+the+accumulation+of+fluid+under+the+retina+in+CSCR,+instead+of+acting+on+its+absorption+as+observed+in+macular+edema+of+other+origins+• Primary+adrenal+cortical+steroid+hormones,+aldosterone+and+cortisol,+act+through+binding+to+the+structurally+similar+mineralocorticoid+(MR)+and+glucocorticoid+(GR)+receptors+• Proposed+that+MR+antagonists+could+be+used+to+treat+CSCR+with+persistent+subretinal fluid+
Daruich A,+ et+ al.+Prog Retin Eye$Res .+ 2015:48:82e118+1 0 9
Mineralcorticoid Antagonists• EplerenoneEFDA+Approved+for+HTN+and+CHF
EHigher+affinity+and+selectivity+than+spironolactone+for+the+MR+E Limited+binding+to+progesterone+and+androgen+receptors+ETypical+dosing;++25mg/day+x+1wk,+then+50mg/day+x+1mo
• SpirnolactoneEFDA+approved+for+hypertensionEInteracts+with+progesterone+receptorsES/E+like+gynecomastia,+ED,+menstrual+irregularitiesEHyperkalemia+in+renal+failure+patients
• Head+to+head+equivalent,+spironolactone+more+s/e
Yang+ D,+Eliott D.+ Semin Ophthalmol. 2017;32:36E42 11 0
January
Images + credit:+ Andrew+ Rixon+ OD,+ FAAO 111
XCSections
Images + credit:+ Andrew+ Rixon+ OD,+ FAAO 112
IVFAs
Images + credit:+ Andrew+ Rixon+ OD,+ FAAO+ and+ Jim+ Williamson+ OD,+ FAAO 113
IVFA(cont….
Images + credit:+ Andrew+ Rixon+ OD,+ FAAO+ and+ Jim+ Williamson+ OD,+ FAAO114
11/28/18
20
Intermediate(Form
Cavallerano,+ Gutner,+ Oshinskie Macular$ Disorders $ 1997 11 5
IVFA(cont….
Images + credit:+ Andrew+ Rixon+ OD,+ FAAO+ and+ Jim+ Williamson+ OD,+ FAAO116
IVFA(cont….
Images + credit:+ Andrew+ Rixon+ OD,+ FAAO+ and+ Jim+ Williamson+ OD,+ FAAO117
Multimodal
Images + credit:+ Andrew+ Rixon+ OD,+ FAAO+ and+ Jim+ Williamson+ OD,+ FAAO118
FAF(and(
Gravity
Shah+ V.+IOVS.2013;54(15):316 4.$
1 1 9
CSCR(Management
• Observation• Eplerenone• Sprinolactone• Conventional+photocoagulation+(OffEfovea+confirmed+by+ICGA)• Subthreshold+Micropulse/PDT• Intravitreals
Goldhagen BE,+ Goldhardt R.+ Curr Ophthalmol Rep$ 2017+ Jun;5(2):141E14812 0
11/28/18
21
CP(Case
1 2 1
CP(2010
• 60yo+AAF+presents+for+postop• s/p+phaco/IOL+OD+x+1day• BCVA++20/30+OD,+20/25E OS• Heart+ disease,+diabetes,+HTN,+Protein+C+Deficiency,+HLD• High+BS+led+to+hospitalization+3yrs+earlier• Meds:+triamterene,+ atenolol,+norvasc,+coumadin,+Insulin,+gabapentin,+coreg,+simvastatin• Oc Hx:++Phaco/IOL+OS+x+2+month
122
RetinalReview
Image+ Courtesy:+Heidelberg
1 2 3
GrayScale is( better!
Image+ credit:+ Andrew+ Rixon+ OD,+ FAAO+ 1 2 4
PEDCHemorrhagic( vs(Serous(
Cavallerano,+ Gutner,+ Oshinskie Macular$ Disorders $ 1997 1 2 5
CP((OS
Image+ credit:+ Andrew+ Rixon+ OD,+ FAAO+ 1 2 6
11/28/18
22
CP
Image+ credit:+ Andrew+ Rixon+ OD,+ FAAO+ 1 2 7
CP
Image+ credit:+ Andrew+ Rixon+ OD,+ FAAO+ 1 2 8
Dx/Management
• Hemorrhagic+PED/PCV• IOA+x+3• Continue+Taper+PF1%+OD+2:1+by+week,+Bromday• Start+ PF1%+qid,+Bromday….consider+IOK+if+NI
129
PCV(Review• AMD+subtype+first+described+in+the+1990s• No+universally+accepted+definition• Initially+considered+Dz of+middle+aged+AA+females• Occur+in+both+sexes,+all+ethnicities,+higher+in+asian vs+caucasian• Characterized+by+recurrent+ serosanguineous maculopathy+and+presence+of+orange+nodules+• Most+base+diagnosis+of+PCV+on+ICGA+findings+that+demonstrate+presence+of+polypoidal dilatations.+(Criterion+differ+per+study)• OCT+structural+and+OCTA+have+not+been+shown+to+supplant+ICGA• Pachychoroid role+in+pathogenesis????
Cheung+ CMG+ et+ al.$Ophthalmology 2018;125:708E724+ 1 3 0
PCV(Problems
Image+credit:+Andrew+ Rixon+OD,+FAAO,+Jim+Williamson+OD,+FAAO,+Michael+White+OD131
OCT(structural(example
Cheung+ CMG+ et+ al.$Ophthalmology 2018;125:708E724+
SD OCT scan (right) with corresponding fluorescein angiography (left) showing a double-layer s ign (black arrowhead), pigment epithelial detachment notch (black arrow), and a thumb-like polyp containing hyperreflective rings with internal hyporeflective lumen (white arrow).
1 3 2
11/28/18
23
EVEREST/PLANET/DRAGON(• Compared+ efficacy+and+ safety+of+antiEVEGF+ to+combo+ PDT/AntiEVEGF
• Found+ that+antiEVEGF+ monotherapy+(IVTER+ or+ IVTEAFL)+ showedESignificant+ VA+ gainESignificant+ polyp+ closure+ ratesESignificantly+ reduced+ disease+ +activity
• Combo+ PDT/AntiEVEGF+ more+effective+than+ monotherapy
• Combo+ required+ fewer+ injectionshttp s://en .wikip ed ia.o rg/wiki/Moun t_ E ve re st #/ med i a/ Fi le:Moun t_ E ve re st _a s_ s een_from_Drukair2 _P LW _ ed it.jp g
1 3 3
Big(Heart(Case
1 3 4
9/2014• 46yo+AAM+who+presents+with+the+loss+of++vision+to+his+left+eye+over+the+last+24+hours.+• Denies+any+pain.++• Patient+states+that+he+was+in+an+MVA+3+days+ago+and+had+some+soreness+to+the+left+side+of+his+body+that+brought+him+into+the+ER+yesterday.++• Patient+left+the+ER+before+his+encounter+was+complete.++Patient+states+that+progressively+over+the+night+he+lost+his+eyesight+at+11:08+PM.+• Denies+any+other+complaints
135
Past(Hx• 5’6”++228lbs• Ischemic+Cardiomyopathy+Dx as+30yo• Htn x+16+yrs (BP+on+first+exam+at+age+33+was+175/122+)• DM+x+15+yrs Avg HbA1C+9%• Hyperlipidemia• (E)+cocaine• CABG+at+41yo+2’+to+80%+stenosis• TIA+c+R+sided+numbness+and+weakness+2013• MRI+2013+Left+thalamic+infarct+noted,+old+CVA
136
3/2014(Photos
Image+ Credit:+ Andrew+ Rixon+ OD,+ FAAO137
9/2014(Photo(OS
Image+ Credit:+ Andrew+ Rixon+ OD,+ FAAO138
11/28/18
24
IVFA/OCT(OD
Image+ credit:+ Andrew+ Rixon+ OD,+ FAAO,+ Michael+ White+ OD,+ Jim+Williamson+ OD,+ FAAO
139
OCT(OS
Image+ cred i t:+And rew+R ixon +OD,+FAAO,+M ichael +Wh ite+OD,+ Jim+Wi l l iamson +OD,+FAAO1 4 0
Middle(Maculopathy(Example
Temporal Nasal
Image+ Credit:+ Andrew+ Rixon+ OD,+ FAAO 141
1min(13(sec(in,(Attention(CRA!!!
Image+ Credit:+Andrew+ Rixon+ OD,+ FAAO
142
IVFAs(OS
Image+ credit:+ Andrew+ Rixon+ OD,+ FAAO,+ Michael+ White+ OD,+ Jim+ Williamson+ OD,+ FAAO143
38(sec….
Image+ credit:+ Andrew+ Rixon+ OD,+ FAAO,+ Michael+ White+ OD,+ Jim+ Williamson+ OD,+ FAAO 144
11/28/18
25
OS(cont….
Image+ credit:+ Andrew+ Rixon+ OD,+ FAAO,+ Michael+ White+ OD,+ Jim+ Williamson+ OD,+ FAAO 145
OS(cont…..
Image+ credit:+ Andrew+ Rixon+ OD,+ FAAO,+ Michael+ White+ OD,+ Jim+ Williamson+ OD,+ FAAO
12+min+9min+
14 6
IVFA(advice?(Ask(Dr.Williamson
23Video+ credit:+ Jim+ Williamson+ OD,+ FAAO 147
CRAO(Review• Causes+infarction+of+the+inner+retina+• Acute,+painless,+catastrophic+vision+loss• 80%+>20/400• Cherry+ red+spot+in+fovea• RGC+infarction+followed+by+progressive+axonal+degeneration+with+pale+optic+atrophy+evident+after+ some+weeks+• NonEarteritic and+arteritic forms• Cause+for+1+in+10,000+outpatient+OMD+visits
Tobalem et+al.+ BMC$ Ophthalmology.+ 2018;18:101Biousse V,+et+ al+Neurol Clin 35+ (2017)+ 83–100
Varma+ DD,+ et+ al.+ Eye (2013)+ 27,+688–697+1 4 8
Retinal(Survival(Time/Heroic(Measures
• Retinal+infarct+likely+to+occur+after+ only+12E15min1
• Historically+between+90E240+min1
• NO+strong+evidence+based+therapy+ exists+for+CRAO+• If+no+retinal+arterial+flow+after+15min+heroic+measures+likely+futile
1)+ Tobalem et+ al.+BMC$ Ophthalmology.+ 2018;18:101+ 1 4 9
AHA/ASA(Definitions
• The+2009+revised+(and+current)+definition+of+a+TIA+“a+transient+episode+of+neurological+dysfunction+caused+by+focal++brain,+spinal+cord,+or+retinal(ischemia,+without+acute+infarction”+
• 2013+(and+current)+Stroke+definition+“Central+nervous+system+infarction+is+defined+as+brain,+spinal+cord,+or+retinal(cell(death(attributable+to+ischemia,+based+on+neuropathological,+neuroimaging,+and/or+clinical+evidence+of+permanent+injury”+
Easton+ JD,+ Stroke.+ 2009;40:2276–2293+Sacco RL,+ Stroke.+ 2013;44:2064–2089+
1 5 0
11/28/18
26
CRAO(and(CVA• 5+year+risk+of+death+from+cerebral+ischemia+post+CRAO+is+11.7%1
• Rate+of+CVA+upwards+of+70x+greater+in+1st week+after+CRAO2
• Acute+ischemic+stroke+detected+in+24%+of+subjects+with+RAO3
• Patients+with+acute+CRAO+should+be+promptly+evaluated+for+stroke+and+stroke+prevention4
• Patients+with+MVL;+TMVL,+CRAO,+BRAO+may+have+up+to+19.5%+risk+of+concurrent+ischemic+stroke5
ENo+concurrent+focal+neurological+s/s• Recommended+to+do+DWI+on+MRI,+CT+misses1) Biousse V,+et+ al+Neurol Clin 35+ (2017)+ 83–100+ 2)Park+ SJ,+ et+ al. Ophthalmology 2015;122:2336E2343+ +3)+ Lee+J,+ et+al.+ Am$ J$Ophthalmol 2014;157:1231–1238+ 4)French+ DD,+ et+al.+ +Ophthalmol Ther.+ 2018+ Mar+ 245)+ Zhang+ +LY,+et+ al.+J+ NeuroEOphthalmol 2018;0:1–6 15 1
So(what’s(the(recommendation?• “Based+on+the+currently+available+literature,+the+treatment+ of+CRAO+should+be+focused+on+identifying+a+concomitant+acute+cerebral+infarction,+which+is+a+medical+emergency;+optimization+of+all+cardiovascular+risk+factors;+and+a+thorough+investigation+for+undiagnosed+cardiovascular+risk+factors,+with+the+ultimate+goal+being+prevention+of+subsequent+ischemic+events,+such+as+an+acute+MI,+vascular+death,+and+acute+cerebral+ischemia.”+• “Optimal+management+of+these+patients+requires+collaboration+between+ophthalmologists+and+stroke+neurologists”+• Note+65%+of+programs+in+a+national+survey+of+teaching+hospitals+routinely+referred+ patients+to+a+general+ER
Biousse V,+et+ al+Neurol Clin 35+ (2017)+ 83–100Youn TS,+J$ Neurol.+ 2018;265:330E335 15 2
Do(you(have(a(Cilioretinal?
1 5 3
CC:
• 59+yo presents+with+c/o+black+spot+in+center+of+vision+x+1+year• Describes+black+spot+as+constantly+being+there• Pt+tilts+head+up+to+see+it• Notes+got+roofing+tar+in+eye++10yrs+previous• Loss+was+sudden• Social:+2packs/day,+homeless• Systemic:
154
Fundus(Photos
Image+ credit:+ Andrew+ Rixon+ OD,+ FAAO+ 1 5 5
ONH(Photos(
Image+ credit:+ Andrew+ Rixon+ OD,+ FAAO+1 5 6
11/28/18
27
VFs
Image+ credit:+ Andrew+ Rixon+ OD,+ FAAO+ 1 5 7Image+ credit:+ Andrew+ Rixon+ OD,+ FAAO+
1 5 8
Macular(Thickness
Image+ credit:+ Andrew+ Rixon+ OD,+ FAAO+1 5 9
XCSections
Image+ credit:+ Andrew+ Rixon+ OD,+ FAAO+ 1 6 0
IVFA
Image+ credit:+ Andrew+ Rixon+ OD,+ FAAO,+ Michael+ White+ OD,+ Jim+ Williamson+ OD,+ FAAO 161
IVFA(cont…
Image+ credit:+ Andrew+ Rixon+ OD,+ FAAO,+ Michael+ White+ OD,+ Jim+ Williamson+ OD,+ FAAO162
11/28/18
28
Case(RK
1 6 3
Case(Hx/Details
• 73yo+WM+for+6mo+eval of+Dry+AMD• Uses+AREDS2+bid• AMD+Dx in+2014• Denies+visual+changes• SysHx:+Smoked+3+packs/day+x+30yrs,+quit+in+1996• SysHx:+Htn,+Obesity• Meds:+HCTZ,+colchicine
164
FP(4/2018(OD
Images + credit:+ Andrew+ Rixon+ OD,+ FAAO+ and+ Michael+ White+ OD165
FP(4/2018 ???
Images + credit:+ Andrew+ Rixon+ OD,+ FAAO+ and+ Michael+ White+ OD166
OCTCA(OvervueOS
Images + credit:+ Andrew+ Rixon+ OD,+ FAAO167
Default(Outer(RetinaCThick(Slices
Images + credit:+ Andrew+ Rixon+ OD,+ FAAO+ 1 6 8
11/28/18
29
Custom(Outer(Retinal(Slice
Images + credit:+ Andrew+ Rixon+ OD,+ FAAO 169
IVFAs(OS
Images + credit:+ +Andrew+ Rixon+ OD,+ FAAO+ and+ Michael+ White+ OD170
IVFAs(OS
Images + credit:+ Andrew+ Rixon+ OD,+ FAAO+ and+ Michael+ White+ OD171
ICGs(OS
Images + credit:+ Andrew+ Rixon+ OD,+ FAAO+ and+ Michael+ White+ OD172
ICGs(OS(cont….
Images + credit:+ Andrew+ Rixon+ OD,+ FAAO+ and+ Michael+ White+ OD173
Case+RG
174
11/28/18
30
Case(History/Exam(details• 74yo+WM+presents+for+annual+doctor+directed+followEup+for+Type+II+DM• No+ocular+complaints• Last+HbA1c=6.9%• Systemic+Hx:+Type+II+DM+x+15yrs,+Hld• Smoker+x+20yrs+ago• Meds:+Glipizide,+Metformin,+Simvastatin,+OmegaE3s• OcHx:+Non+visually+significant+cataracts+(E)retinopathy• BCVA+OD:+20/20,+OS:+20/25• SLE:++2++NS,+2++Cortical• Images+to+Follow………
175
Representative(PhotoCNot(our(Patient
1 7 6
XCsections(OD
1 7 7
XCsections(OS
1 7 8
EDI(XCSections ELM PIL/Ellipsoid+Line
RPEBruch’s Subretinal???179
FAF
1 8 0
11/28/18
31
Reticular(Pseudodrusen (RPD)
• 1st described+in+1990+as+yellowish+and+illEdefined+interlacing+network+on+clinical+examination+and/or+fundus+photography• Now+known+as+subretinal drusenoid deposits+• Appear+as+an+orderly+array+ of+relatively+white,+dotElike+accumulations+• RPD+give+a+4E8x+increased+risk+of+5yr+progression+to+late+AMD• Risk+is+independent+of+conventional+drusen and+focal+pigmentary+abnormalities.+
IOVS. 2016;57:1310–1316 Surv Ophthalmol 61 (2016) 521e537
Surv Ophthalmol 61 (2016) 521e537 1 8 1
RPD(vs(Drusen
IOVS. 2016;57:1310–1316
RPE 1 8 2
RPD(stages
Surv Ophthalmol 61 (2016) 521e537 1 8 3
AutofluorescenceCRPD
Image+ Credit:+ Andrew+ Rixon+ OD,+ FAAO184
Other(Eye
Image+ Credit:+ Andrew+ Rixon+ OD,+ FAAO 185
Drusen Regression
Opthalmology 2016;123:39E50 Image+ Credit:+ Drew+ Rixon+ OD,+ FAAO186
11/28/18
32
Construction(Case
1 8 7
Case(details( CH• 55yo+WM• Cc:+Constant+ blur+ at+distance+ and+near+ OD>>OS• Vision+ started+ worsening+ over+ last+ year+but+ has+been+ bad+ at+near+ for+11+ +years
• OcHx:+Pt+notes+ hit+ head+ frequently+ when+ worked+ construction• SysHx:+(+)MI+2mo+ previously,+ (+)DVT+ Dx 2mo+previously• Social:+ ½+pack+per+day• BCVA:+ 20/50E OD,+ 20/20+ OS• Trace+APD+ OD• SLE+unremarkable• Posterior+ attached
188
Fundus(Photography
Courtesy+ Mohammad+ “The+ great+ one”+ RafieetaryOD,+ FAAO+ +Charles + Retina+ Institute
1 8 9
Shields(B(Scan…..
Shields + CL,+et+ al.$ Ophthalmology$ 2001;108:2237–2248$1 9 0
Our(Patient’s(B(Scan• “3.0+mm+apically+elevated,+8mm+basal+diameter+choroidal+lesion+with+high+internal+reflectivity,+homogenously+hyperechoic/acoustically+solid”
191
FAF
Image+ credit:+ Andrew+ Rixon+ OD,+ FAAO,+ Michael+ White+ OD,+ Jim+ Williamson+ OD,+ FAAO Ramasubramanian A,+ et+ al.+Retina.+ 2010;30:16E22
19 2
11/28/18
33
EDI(XCsection
Image+ credit:+ Andrew+ Rixon+ OD,+ FAAO 193
EDI(XCsection
Image+ credit:+ Andrew+ Rixon+ OD,+ FAAO194
FAs
Image+ credit:+ Andrew+ Rixon+ OD,+ FAAO,+ Michael+ White+ OD,+ Jim+ Williamson+ OD,+ FAAO 195
Fas cont….
Image+ credit:+ Andrew+ Rixon+ OD,+ FAAO,+ Michael+ White+ OD,+ Jim+ Williamson+ OD,+ FAAO 196
FAs(cont….
Image+ credit:+ Andrew+ Rixon+ OD,+ FAAO,+ Michael+ White+ OD,+ Jim+ Williamson+ OD,+ FAAO197
ICGs
Image+ credit:+ Andrew+ Rixon+ OD,+ FAAO,+ Michael+ White+ OD,+ Jim+ Williamson+ OD,+ FAAO 198
11/28/18
34
Dx and(Management• Circumscribed+Choroidal+Hemangioma+• Referral+ to+Retina• Patient+has+since+undergone;
EIOA+x+4EPDT+x+2EFocal+photocoagulation
• Last+retinal+eval showed+“Minimal+improvement+on+repeated+PDT+and+antiEVEGF”• BCVA+20/80E• Referral+ to+oc oncology+for+possible+low+dose+plaque+brachytherapy
199
Choroidal(Hemangioma(Review• Rare+ Vascular+tumor+(5%+of+pseudomelanomas)+• Unknown+cause• Likely+congenital,+• Typically+asymptomatic+until+4thE6th decade• Unknown+prevalence/Most+asymptomatic• No+correlation+with+systemic+disease• Composed+of+choroidal+vessels+but+spares+choriocapillaris• Slow+to+no+progression+in+size+over+time• Within+1+to+3+DD+of+the+macula• Ranges+from+3E19+mm+in+diameter+and+1E8mm+in+thickness
Berry+ M,+ Lucas +L.+Journal$ of$ Optometry$ (2017)+ 10,(79E83+Karimi S,+et+ al.+J$Ophthalmic$ Vis $Res $2015;+ 10+(3):+ 320E328.+
Shields + CL,+et+ al.+ Ophthalmology$2001;108:2237–2248$
2 0 0
What(would(Carol(Shields(Do?• Not+sure+but+the+options+are…..
EObservation+in+asymptomatic+s+SRFEPDTETx of+choice+for+symptomatic+c+detachmentELaser+photocoagulationEPlaque+brachytherapyEExternal+beam+and+proton+beam+radiationESterotactic radiosurgeryETranspupillary thermotherapyEOral+propranolol+EEnucleation
http s://twitter.com/sea rch ?q=%2 3 ch iefs round s
Karimi S,+et+ al.+J$Ophthalmic$ Vis $Res $2015;+ 10+(3):+ 320E328Berry+ M,+ Lucas +L.+Journal$ of$ Optometry$ (2017)+ 10,(79E83+ 2 0 1
Metastatic(Tumor(on(Ultrasound
Image+ credit:+ Andrew+ Rixon+ OD,+ FAAO
Image+ credit:+ Andrew+ Rixon+ OD,+ FAAO202
Metastatic(Melanoma
Image+credit:+Andrew+ Rixon+OD,+FAAO
203
XCRay/MRI
Image+credit:+Andrew+ Rixon+OD,+FAAO204
11/28/18
35
Melanoma/Melanoma( on(B(scan
Myelination
RPE+Reactive+Hyperplasia
Choroidal+Mass
Shields CL, et al. Curr Opin Ophthalmol 2014, 25:177 – 185
Clinical$ Ophthalmology$ 2017:11+ 1557–1564+Neuroimag Clin N$Am$ 25+ (2015)+ 327–365+
2 0 5 2 4 6