Optical Coherence Tomography Angiography in Retinal Diseases

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1 [Downloded free from on Wednesdy, April 20, 2016, IP: ] Review Artile Optil Coherene Tomogrphy Angiogrphy in Retinl Diseses K. V. Chlm, MD, PhD; Kumr Smhv, MD Deprtment of Ophthlmology, University of Florid College of Mediine, Florid, USA Astrt Optil oherene tomogrphy ngiogrphy (OCTA) is new, non invsive imging system tht genertes volumetri dt of retinl nd horoidl lyers. It hs the ility to show oth struturl nd lood flow informtion. Split spetrum mplitude deorreltion ngiogrphy (SSADA) lgorithm ( vitl omponent of OCTA softwre) helps to derese the signl to noise rtio of flow detetion thus enhning visuliztion of retinl vsulture using motion ontrst. Pulished studies desrie potentil effiy for OCTA in the evlution of ommon ophthlmologi diseses suh s dieti retinopthy, ge relted mulr degenertion (AMD), retinl vsulr olusions nd sikle ell disese. OCTA provides detiled view of the retinl vsulture, whih llows urte delinetion of mirovsulr normlities in dieti eyes nd vsulr olusions. It helps quntify vsulr ompromise depending upon the severity of dieti retinopthy. OCTA n lso eluidte the presene of horoidl neovsulriztion (CNV) in wet AMD. In this pper, we review the knowledge, ville in English lnguge pulitions regrding OCTA, nd ompre it with the onventionl ngiogrphi stndrd, fluoresein ngiogrphy (FA). Finlly, we summrize its potentil pplitions to retinl vsulr diseses. Its urrent limittions inlude reltively smll field of view, inility to show lekge, nd tendeny for imge rtifts. Further lrger studies will define OCTA s utility in linil settings nd estlish if the tehnology my offer non invsive option of visulizing the retinl vsulture, enling us to derese moridity through erly detetion nd intervention in retinl diseses. Keywords: Optil Coherene Tomogrphy Angiogrphy (OCTA); Split-spetrum Amplitude Deorreltion Angiogrphy (SSADA); Dieti Retinopthy; Age Relted Mulr Degenertion; Choroidl Neovsulriztion J Ophthlmi Vis Res 2016; 11 (1): INTRODUCTION Optil oherene tomogrphy (OCT) hs emerged s n importnt imging modlity in the evlution nd Correspondene to: K. V. Chlm, MD, PhD. Deprtment of Ophthlmology, University of Florid College of Mediine, 580 West 8 th Street, Tower 2, 3 rd Floor, Jksonville, FL 32209, USA. E mil: khlm@jx.ufl.edu Reeived: Aepted: Quik Response Code: Aess this rtile online Wesite: mngement of retinl diseses. The noninvsive nture of the test nd its ility to imge introulr strutures in vivo with resolution pprohing tht of histologil setions hs mde OCT prtiulrly useful for detetion nd quntifition of mulr nd opti nerve hed pthologies. [1] Reently, severl OCT sed ngiogrphy methods hve een developed for noninvsive 3 dimensionl vsulr mpping t the miroirultion level. [2] Optil oherene tomogrphy ngiogrphy (OCTA) This is n open ess rtile distriuted under the terms of the Cretive Commons Attriution NonCommeril ShreAlike 3.0 Liense, whih llows others to remix, twek, nd uild upon the work non ommerilly, s long s the uthor is redited nd the new retions re liensed under the identil terms. For reprints ontt: reprints@medknow.om DOI: / X How to ite this rtile: Chlm KV, Smhv K. Optil oherene tomogrphy ngiogrphy in retinl diseses. J Ophthlmi Vis Res 2016;11: Journl of Ophthlmi nd Vision Reserh Pulished y Wolters Kluwer Medknow

2 [Downloded free from on Wednesdy, April 20, 2016, IP: ] OCT Angiogrphy in Retinl Diseses; Chlm nd Smhv is new non invsive imging tehnique tht employs motion ontrst imging to high resolution volumetri lood flow informtion generting ngiogrphi imges in mtter of seonds. The use of the split spetrum mplitude deorreltion ngiogrphy (SSADA) lgorithm [3] improves the signl to noise rtio of flow detetion; thus the pplition of this lgorithm in OCTA n ssist visuliztion retinl vsulture. [4,5] COMPARISON OF OCTA WITH FUNDUS FLUORESCEIN ANGIOGRAPHY (FFA) Fundus fluoresein ngiogrphy (FA) is vitlly importnt dignosti tool for evluting ptients with retinl pthologies. It is n invsive test tht requires intrvenous dministrtion of dye nd imging for t lest10 15 minutes. FA provides two dimensionl imge sets tht llow dynmi visuliztion of lood flow with wide field of view; therefore, ptterns of dye lekge, pooling, nd stining n e ppreited nd re well doumented in the literture. [6] However, FA nnot seprtely visulize the intrretinl strutures of mjor pillry networks; the imges of superfiil nd deep pillries overlp, so 2 of the 3 mjor pillry networks (superfiil retinl, deep retinl nd horiopillries) do not pper to e imged well despite the retin eing nerly trnsprent struture. [5] Weinhus et l [7] hve reported tht FA does not imge the deeper pillry plexus well in monkey eyes. FA hs other drwks tht n limit its widespred use; it is invsive, reltively expensive, time onsuming, nd not n idel tehnique for use on regulr sis in usy linil setting. Although onsidered sfe, the dye poses risks rnging from nuse to llergi retions, inluding nphylxis in rre instnes. For evlution of ptients requiring frequent follow up exmintions or those tht my not tolerte injetion of the intrvenous dye, rpid non invsive tehnique to visulize retinl nd horoidl vessels would e enefiil. OCTA, in omprison, is non invsive tehnique tht quires volumetri ngiogrphi informtion without the use of dye. Eh three dimensionl sn set tkes pproximtely six seonds to otin. The en fe imges otined n then e srolled to visulize individul vsulr plexuses nd segment the inner retin, outer retin, horiopillris, or other res of interest. Spide et l [2] hve demonstrted tht FA does not imge the rdil perippillry or the deep pillry networks well. However, OCT ngiogrphy n imge ll lyers of the retinl vsulture without dye injetion [Figure 1-]. PRINCIPLES OF OCTA The most widely ville prototype system of OCTA is the RTVue XR Avnti (Optovue In., Fremont, Cliforni, USA). This instrument hs n A sn rte of 70,000 sns per seond, using light soure entered on 840 nm nd ndwidth of 50 nm. The tissue resolution is 5 mm xilly nd there is 15 mm em width. Imge Aquisition Figure 1. Comprison of imges of fundus floresene ngiogrphy () to OCTA imges of superfiil plexus ( nd ) in norml sujet. Erly imges of FA (15.2 se) shows norml fillings of rteries nd veins. OCTA (6 6 mm) of superfiil plexus () showing norml pillry network with etter resolution of smller pillry network. OCTA (3 3 mm) of superfiil plexus () showing ler delinetion of fovel vsulr zone nd well defined pillry network. Two sets of imging re performed t one ssessment. Eh imge set omprises of two rster volumetri ptterns (one vertil priority nd one horizontl priority) overing options of 2 2 mm, 3 3 mm, 6 6 mm, nd 8 8 mm. An orthogonl registrtion lgorithm (in uilt softwre whih hs the ility to orret some motion rtifts) is used to produe merged 3 dimensionl OCT ngiogrms. Eh volume set is omposed of 216 line sn lotions t whih 5 onseutive B sns were otined. The results of 2 sets of imges otined re verged using inuilt softwre. Split spetrum Amplitude Deorreltion Angiogrphy (SSADA) The SSADA lgorithm ompres onseutive B sns otined t the sme lotion to detet lood flow in vessels using motion ontrst. [2 5] After proessing the volume sns, deorreltion of the imges (1 orreltion), is lulted. The imging hrteristis of the sn for sttionry tissues, show high orreltion from one frme to the next. However, imging hrteristis of lood flowing through vessels hnge refletne over suessive sns using low orreltion etween frmes (or high deorreltion). The resultnt orrelted frmes re evluted nd sttistil outliers re removed to redue the possiility of tissue motion rtifts. Furthermore, the spetrum of the light soure is split Journl of Ophthlmi nd Vision Reserh 2016; Vol. 11, No. 1 85

3 [Downloded free from on Wednesdy, April 20, 2016, IP: ] OCT Angiogrphy in Retinl Diseses; Chlm nd Smhv into 4 omponents to derese the noise present in the imge nd eh omponent is then used to perform the deorreltion step seprtely. Finlly, the results of ll 4 omponents re verged nd lok of informtion is generted tht ontins the levels of deorreltion (rnging from 0 to1). This split spetrum strtegy trdes some of the xil resolution for deresed noise nd for higher trnsverse resolution. Segmenttion nd Perfusion Indies of OCT Angiogrphy Imge The retin is lminr struture with orresponding strtifition of lood supply nd retinl segmenttion into speifi lyers llows en fe visuliztion of the orresponding vsulr supply for tht lyer. In uilt utomted softwre proesses the imge informtion generting sets of perfusion indies (vessel density nd flow index) for four en fe setions of the retin. Vessel density is defined s the perentge re oupied y vessels in the segmented re nd flow index is defined s the verge deorreltion vlues in the segmented re. The 4 en fe zones inlude: i) The superfiil plexus, the pillry network in gnglion ell lyer; ii) the deep plexus, network of pillries etween the outer oundry of the inner plexiform lyer nd the midpoint of the outer plexiform lyer (totl thikness, 55 mirons); iii) the outer retin (photoreeptors), does not hve vessels, however, perfusion indies re still otined, nd iv) the horiopillries (horoid) with offshoot of 30 mirons [Figure 2]. For eh one of the en fe zones, the softwre quires perfusion indies seprtely in prfovel (entrl, 3 mm) nd perifovel (etween 3 6 mm) res [Figure 3]. Centrl pillry free fovel vsulr zone (FAZ) is exluded utomtilly from mesurements of the perfusion indies. However, vlues for FAZ re (mm2) n e otined in the entrl re using the in uilt softwre [Figure 4 nd ]. Figure 2. The lotion of different en fe zones in reltion to histology of the humn retin. The four en fe zones inlude, (i) the superfiil plexus, the pillry network in gnglion ell lyer nd nerve fier lyer; (ii) the deep plexus, network of pillries in the inner plexiform lyer with offshoot of 55 miron; (iii) the outer retin (photoreeptors), nd (iv) the horiopillries (horoid) with offshoot of 30 mirons. 86 ARTIFACTS WITH OCTA In ny imging system used in mediine, the imge formed of tissue psses through series of rules. Unfortuntely, even with the est imging method, the imge is not perfet nd there re extr or missing piees of informtion or trnsltion, lled rtifts. Spide et l[8] desried vrious rtifts seen in OCTA imges. These rtifts our due to OCT imge quisition, intrinsi hrteristis of the eye, eye motion, imge proessing, nd disply strtegies. Beuse of the potentil of rtifts, linil evlution long with viewing of the imge is usully required for interpreting the results, muh like wht hppens in modern rdiology prtie. In the usul linil settings, imges otined y OCTA re exluded from nlysis or interprettion if they hve: i) Poor qulity (with signl strength index 40) or ii) residul motion rtifts (disontinuous vessel pttern or hzy imges). OCTA IN NORMAL EYES Despite the use of newly ville OCTA, there is limited informtion on normtive dtse nd its ppliility in retinl pthologies. Mtsung et l[9] in series on 5 helthy sujets reported tht OCTA genertes high resolution, noninvsive ngiogrms qulittively Figure 3. Grphil representtion of 4 en fe zone. Eh enfe zone is divided into inner prfovel (1 3 mm) nd outer perifovel (3 6 mm) regions. Perfusion indies (vessel density nd flow index) re otined seprtely for perifovel nd prfovel regions spring entrl fovel vsulr zone of 1 mm. Journl of Ophthlmi nd Vision Reserh 2016; Vol. 11, No. 1

4 [Downloded free from on Wednesdy, April 20, 2016, IP: ] OCT Angiogrphy in Retinl Diseses; Chlm nd Smhv Figure 4. Optil oherene tomogrphy ngiogrphy (OCTA) of the fovel vsulr zone (FAZ) otined using inuilt softwre (mm 2 ). () FAZ re in the superfiil plexus of norml sujet; () the FAZ re otined in the deep plexus of norml sujet. omprle to onventionl fluoresein ngiogrphy in norml sujets. The fove is histologilly omprised of region solely ontining ones with elongted outer segments underlying pillry free zone, designted s the FAZ. A numer of studies on norml popultion hve demonstrted vritions in fovel thikness, FAZ shpe, nd FAZ re. [10 13] The humn retinl pillry network is omposed of distint lyers of vessels nd pillries inluding the superfiil (inner), nd the deep (outer) vsulr plexus. [14] Smr et l [15] desried the use of OCTA for mesurement of the FAZ re (using Imge J softwre, Wyne Rsnd, Ntionl Institutes of Helth, Bethesd, Mrylnd, USA) of oth the superfiil nd deep pillry plexuses in 70 helthy eyes nd determined orreltions with ge nd sex. They reported tht the FAZ re is vrile in the norml popultion with men vlues of ± mm 2 in the superfiil plexus (rnge, mm 2 ) nd ± mm 2 in the deep plexus (rnge, mm 2 ). FAZ re ws signifintly lrger in the deep plexus (P < ) s ompred to the superfiil plexus. No signifint orreltion ws found etween the re of the superfiil or deep plexus FAZ, nd ge or sex. Svstno et l [16] desried retinl vsulr ntomy y OCTA in 52 helthy eyes y nlyzing the morphologi fetures of the superfiil nd deep networks. They reported existene of seprte vsulr networks in the inner retin: The superfiil network (in the nerve fier lyer nd the gnglion ell lyer) nd the deep network (in the outer plexiform lyer). Both networks were interonneted with numerous vertil vessels. OCTA IN DIABETICS Dieti retinopthy (DR) is one of the leding uses of lindness worldwide nd ptients tormented with this sight thretening disese re expeted to grow s dietry hits re hnging espeilly in developing ntions. OCTA hs lredy shown promise in eing le to identify hnges in DR. [17] Ishizw et l [18] reported tht OCTA n lerly visulize mironeurysms nd res of retinl non perfusion enling loser oservtion of eh lyer of the retinl pillries; therefore OCTA my e linilly useful to evlute the mirovsulr sttus nd effetiveness of tretments for DR. Agemy et l [19] desried progressive hnges in DR s n esy quntittive interprettion of hnges in retinl vsulrity [Figure 5 ]. They hve shown signifint derese in retinl pillry perfusion density with inrese in severity of DR [Figure 6 d]. de Crlo et l [20] onduted study on 61 eyes with dietes mellitus with no linil dieti retinopthy nd 28 ontrol eyes of helthy sujets nd reported tht OCTA ws le to imge fovel mirovsulr hnges not deteted y linil exmintion. FAZ re ws ( ) mm 2 in dieti eyes nd ( ) mm 2 in ontrol eyes (P = 0.04). FAZ remodeling ws seen more often in dieti thn in ontrol eyes (36% vs. 11%) nd so ws pillry nonperfusion (21% of dieti eyes vs. 4% of ontrol eyes). Tkse et l [21] hve lso reported vritions in the FAZ res in dieti eyes with nd without dieti retinopthy. The FAZ re in the superfiil lyer ws 0.25 ± 0.06 mm 2 in 19 helthy eyes, 0.37 ± 0.07 mm 2 in 24 dieti eyes without retinopthy nd 0.38 ± 0.11 mm 2 in 20 eyes with DR. Dieti eyes showed sttistilly signifint FAZ enlrgement ompred to helthy eyes, irrespetive of the presene of DR [Figure 7 d]. OCTA IN AMD Age relted mulr degenertion (AMD) is the leding use of irreversile vision loss in the United Sttes in the 65 yers nd older ge group. AMD is rodly lssified into wet (exudtive) nd dry forms. Wet AMD is herlded y the formtion of horoidl neovsulr memrne (CNV), it ounts for pproximtely 15% of AMD ses nd mkes up the mjority of ses with vision loss. [22] Wet AMD is lssified into 3 types. Type I CNV (oult), the most ommon type, origintes in the horoid nd extends minly etween Bruh s memrne nd the retinl pigment epithelium (RPE). Type II CNV extends etween the RPE elow nd retin ove (the lest ommon type). Type III CNV lso lled retinl ngiomtous prolifertion (RAP) is the seond most ommon form of wet AMD. [23] Plejwl et l [24] reported the ppliility of OCTA for erly detetion of CNV. In their series, they were le to detet erly CNV (type I), whih ws diffiult to identify using onventionl FA nd SD OCT. El Ameen et l [25] hrterized Type II CNV using OCTA. In their ohort of 14 ptients, ll demonstrted hyperflow vsulr lesion in the outer retin, with glomerulus (4/14) or medus shpe (10/14), surrounded y drk hlo, proving tht OCTA Journl of Ophthlmi nd Vision Reserh 2016; Vol. 11, No. 1 87

5 [Downloded free from on Wednesdy, April 20, 2016, IP: ] OCT Angiogrphy in Retinl Diseses; Chlm nd Smhv Figure 5. Imges of ptient with non prolifertive dieti retinopthy ut no mulr edem. () Mulr thikness mp using spetrl domin optil oherene tomogrphy (SD OCT). () Conventionl fluoresein ngiogrphy (FA) with leking miro neurysm nd ishemi temporl to the fove. () optil oherene tomogrphy ngiogrphy (OCTA) imge of the superfiil plexus of the sme ptient shows etter delinetion of the ishemi re s ompred to FA. d Figure 7. Imge of ptient with mild non prolifertive dieti retinopthy nd dieti mulr edem. ( nd ) Showing the en fe imge of the superfiil plexus with distortion of fovel vsulr zone (FAZ). ( nd d) Showing the en fe imge of the deep plexus with distortion of FAZ, more profound thn in superfiil plexus. This hppens due do umultion of fluid in retinl lyers. is highly sensitive in deteting CNV [Figure 8 ]. There re reports[26,27] where OCTA hs een le to identify distint neovsulr omplex in RAP lesions. The neovsulr omplex of RAP ppers s smll tuft of right, high flow tiny vessels with urviliner morphology loted in the outer retinl lyers with feeder vessel ommuniting with the inner retinl irultion. Coss et l[28] evluted 80 eyes with wet AMD using OCTA snning nd identified different ptterns of CNV. Their ohort lso underwent trditionl multimodl imging, sed on FA, indoynine green ngiogrphy (ICGA), nd spetrl domin OCT (SD OCT) to ssess the need for tretment. Bsed on OCTA findings, they lssified wet AMD into two ptterns. Pttern I, if it showed ll or t lest three of the following five fetures. 1) A well defined (ly wheel or se fn shped) CNV lesion in ontrst to one with long 88 d Figure 6. Imges of ptient with mild non prolifertive dieti retinopthy ( nd ) in omprison to ptient with severe non prolifertive dieti retinopthy ( nd d). There is derese in perfusion indies (vessel density nd flow index) s the severity of dieti retinopthy inreses. Figure 8. Optil oherene tomogrphy ngiogrphy (OCTA) of ptient with CNV (mixed type) with orresponding spetrl domin OCT. () The OCTA imge of superfiil plexus, with ssoited fovel ysti hnges. () Medus hed pperne of neo vsulr (NV) memrne in the photoreeptor zone (white rrows). () NV memrne extends in the deeper horoid (red rrows) with extensive roriztion. filmentous liner vessels. 2) Brnhing, numerous tiny pillries, typil of reent lesion, in ontrst to rre lrge mture vessels, typil of mture one. 3) Presene of nstomoses nd loops. 4) Morphology of the vessel termini, ssessing the presene of peripherl rde in ontrst to ded tree pperne. 5) Presene of perilesionl hypointense hlo onsidered s regions of horiopillris ltertion, either orresponding to flow impirment stel or lolized trophy. A perilesionl hypointense hlo ws only reported to e visile in n en fe setion externl to Bruh s memrne, nd fter exlusion of possile msking effets due to Journl of Ophthlmi nd Vision Reserh 2016; Vol. 11, No. 1

6 [Downloded free from on Wednesdy, April 20, 2016, IP: ] OCT Angiogrphy in Retinl Diseses; Chlm nd Smhv intrretinl, suretinl or su RPE lood, nd fluid or pigment umultion. A CNV lesion ws onsidered s Pttern II, if it showed less thn three of the previously reported OCTA fetures. Ji et l [4] reported tht OCTA n provide depth resolved informtion of CNV nd quntittive informtion regrding CNV flow nd re. Moult et l [29] demonstrted horiopillris ltertions surrounding the CNV. de Crlo et l [30] desried hrteristis s well s the sensitivity nd speifiity of detetion of CNV using OCTA. In their ohort of 48 eyes, speifiity of CNV detetion on OCTA s ompred with FA ws high (91%) ut sensitivity ws 50% (4/8). Monthly injetions of nti vsulr endothelil growth ftor (VEGF) gents is highly suessful nd urrently the tretment of hoie for wet AMD. [31] Lumroso et l [32] oserved morphologi hnges of CNV vessels using OCTA, over weeks fter tretment with intrvitreous nti VEGF injetions nd noted lternting regression nd progression phses. Twenty four hours fter injetion, there ws derese in the dimensions of CNV with loss of smller vessels nd nrrowing of lrger vessels. Between dys 7 nd 12, there ws ontinued derese in the size of CNV, wheres the entrl trunk remined unhnged. The mximum derese in vessels ws noted etween dys 13 nd 18. Re prolifertion ws noted fter dy 28 [Figure 9 f]. OCTA IN IDIOPATHIC MACULAR TELANGIECTASIA Mulr telngietsi Type 2 (MTel2) is disese of the mulr re, in whih neurodegenertive hnges (loss of Muller ells) ply entrl role. [33 35] Anormlities in the MTel re inlude whitening of the inner retin, rystl deposits in the nerve fier lyer, rekdown of the externl limiting memrne/ellipsoid zone, yst formtion in the inner retin, vittion of the outer retin, perifovel pillry lekge, prfovel venulr diltion, pigment prolifertion in the retin, nd suretinl neovsulriztion. [36] Zeimer et l [37] ttempted to estlish n ssoition etween morphologi findings noted on OCTA nd FA in ptients with MTel type 2. On OCTA, they noted retinl vsulr pthology in the deep pillry network inluding enlrgement of vessels nd lrger intervsulr spes, dilted, dendriti pperne of vessels, telngietsis, redution nd/or loss of pillry density, nd the presene of nstomoses towrd the superfiil pillry network. Vsulr hnges ould pper t ny stge of the disese. RPE prolifertions were often ssoited with ontrtion of surrounding vessels. Their OCTA finding showed omprle results to tht of vsulr hnges in FA, proposing etti pillries minly in the deeper pillry network in erly stges of the disese. With progression of disese, vsulr hnges were noted in the superfiil pillry network. Lter, new vessels were seen in the vsulr outer retin nd n irregulr pttern ppered in the underlying horiopillris. OCTA IN RETINAL VESSEL OCCLUSION d e Figure 9. Optil oherene tomogrphy ngiogrphy (OCTA) imges of ptient with horoidl neovsulriztion (CNV) efore ( ) nd 2 weeks fter tretment with nti VEGF (d f). () OCTA imge of the deep plexus, with ysti hnges using olitertion of vsulr refletion. () NV memrne in the photoreeptor zone. () NV memrne extending in the deeper horoid. (d) OCTA of the deep retinl plexus fter tretment with nti VEGF. Vessels in the deeper retinl plexus re etter visulized due to regression of ysti hnges. (e) Regression of the NV memrne in the photoreeptor zone. Olitertion of smller vessels nd derese in the size of min feeder trunk is noted. (f) Regression in the size of NV memrne is lso noted in the horiopillry lyer. f Retinl vein olusions (RVOs) re one of the mjor uses of vision loss nd impirment. The ommonly epted pthophysiology of entrl retinl vein olusion (CRVO) nd rnh retinl vein olusion (BRVO) is thromosis of the retinl vein, leding to vrily impired pillry perfusion nd retinl ishemi. [38] Kshni et l [39] reported findings in OCTA of 26 eyes with RVO. They showed tht OCTA findings were onsistent with linil, ntomi nd fluoresein ngiogrphi findings inluding res of impired vsulr perfusion, retinl trophy, vsulr diltion, shunt vessels, nd some forms of intrretinl edem. Hene, OCTA in onjuntion with SD OCT ould e t lest eqully effetive s FA for evlution nd mngement of mulr omplitions in ptients with retinl vein olusions [Figure 10 ]. Bonini Filho et l [40] desried the retinl mirovsulture of eyes with Journl of Ophthlmi nd Vision Reserh 2016; Vol. 11, No. 1 89

7 [Downloded free from on Wednesdy, April 20, 2016, IP: ] OCT Angiogrphy in Retinl Diseses; Chlm nd Smhv Figure 10. Comprison of fluoresein ngiogrphy imge () in rnh retinl vein olusion with tht of optil oherene tomogrphy ngiogrphy (OCTA) imges otined t the superfiil () nd deep () retinl plexus. Ishemi re due to pillry drop out is etter delineted using OCTA. However, leking vessels due to neovsulriztion re not identified using OCTA. nonrteriti retinl rtery olusion (RAO) sed on OCTA nd onluded tht OCTA n urtely disern retinl pillry plexuses t different levels in eyes with RAO. OCTA my e sensitive enough for hrterizing the extent of mulr ishemi nd monitoring vsulr flow hnges during the ourse of RAO. MISCELLANEOUS CONDITIONS OCTA in Sikle Cell Retinopthy In symptomti sikle ell retinopthy, SD OCT shows temporl mulr thinning, [41] the use of whih is not well understood. Histopthologi studies of sikle ell retinopthy nd other vso olusive diseses hve shown seletive trophy of inner retinl lyers (gnglion ell lyer, inner nuler lyer, nd Müllerin gli of the retin) in severl eyes fter retinl infrtion. [41] Hn et l [42] reported tht OCTA is proly more sensitive thn FA in identifying these erly res of non perfusion in ptients with sikle ell disese where ltertion of the deep pillry network is noted [Figure 11 ]. OCTA in Centrl Serous Chorioretinopthy Idiopthi entrl serous horioretinopthy (ICSC) typilly ffets the young nd middle ged popultion. Ptients usully develop one (or sometimes more) smll re (s) of serous dethment of RPE in the mul or prmulr re, generlly ssoited with serous dethment of the overlying nd surrounding retin. Demonstrtion of ICSC is sed on ngiogrphi pooling of suretinl fluid, pperne of defets in the RPE, nd typil dye lekge from the horoid into the suretinl spe. Most ses hve good prognosis with spontneous resolution long with good visul reovery. However, few n hve ompromised visul outome. This n e due to the reurrent nture of the disese or to development of seondry neovsulr memrnes. Bonini Filho et l [43] reported tht OCTA hs high sensitivity nd speifiity; omprle to FA for detetion of CNV in eyes with hroni ISCR. Figure 11. Conventionl fluoresein ngiogrphy (FA, ) in omprison to optil oherene tomogrphy ngiogrphy (OCTA) imges of the superfiil () nd deep () plexus in ptient with sikle ell disese. Temporl re of thinning (onfirmed using spetrl domin OCT) showed pillry dropout on OCTA, whih is not s lerly visile on FA. () Temporl re of vsulrity in superfiil plexus, lulted using in uilt softwre ws mm 2. () Temporl re of vsulrity lulted using in uilt softwre in deep plexus ws mm 2. Limittions of OCTA Despite the potentil enefits of OCT ngiogrphy, our expettions of tehnology must e tempered, given our limited experiene. With ny new tehnique, we must first vlidte the ury nd reproduiility of the dt. A lrge multi entri multi ethni study ompring this modlity with FA my lso e instrutive in order to etter understnd the signifine of vsulr ptterns oserved with OCTA nd to orrelte this to sites of lekge. A mjor hllenge is to develop utomted repetle segmenttion lgorithms tht relily identify speifi retinl vsulr lyers, even in the disesed nd poorly fixting eyes. At this time, the identifition of neovsulr tissue must e performed mnully, time onsuming tsk s ompred with review of FA imges. Further limittions inlude suoptiml orretion for eye motion rtifts nd projetion rtift from superfiil vessels during imging of deeper lyers. Distinguishing pthologi vessels from the norml vsulture my e hllenging in ertin ses. Moreover, the SSADA tehnique hs reltively poor xil resolution (~15 μm) due to signl verging, limiting the identifition of smll lier vessels. Using the urrent ommerilly ville tehnology, OCTA is more prone to rtifts thn FA. The lrger superfiil retinl vessels use ghost imge produing shdow rtifts, when segmenting deeper lyers, espeilly in the outer retin. This n mke it more diffiult to ppreite the presene of norml vsulture in deeper lyers nd hve ering on perfusion index. Beuse OCTA uses the priniple tht movement in the k of the eye represents lood flow, it is prone to motion rtift. White lines (representing deorreltion signls) pper in res of the sn if the ptient loses fixtion or moves. Conversely, links pper s lk line ross the sn euse the OCT signl is loked from rehing the retin nd 90 Journl of Ophthlmi nd Vision Reserh 2016; Vol. 11, No. 1

8 [Downloded free from on Wednesdy, April 20, 2016, IP: ] OCT Angiogrphy in Retinl Diseses; Chlm nd Smhv the softwre, thus, detets no movement. Blood ells should e the only moving ojet in the retin nd some non vsulr strutures suh s fine tissue my lso use deorreltion signl, espeilly if the ptient is moving or poorly fixting. OCTA my lso miss res of slow lood flow suh s in mironeurysms or firoti CNV. Sine OCTA relies on hnges etween onseutive B sns, it will detet flow only ove minimum threshold, the slowest detetle flow, whih is determined y the time etween the two sequentil OCT B sns. Consequently, lesions whih hve flow elow the slowest detetle flow nnot e visulized using this imging tehnique. Inresing the time etween onseutive OCT B sns ould llow for inresed flow detetion while it would offer trde off due to inresed movement rtift. Finlly, it remins unknown how the dditionl informtion gined from this tehnique n e used in routine linil prtie. The Future of OCTA This powerful feture hs enormous implitions for understnding tissue perfusion in the sene of ovious morphologil hnges. A flow index of the retin nd opti nerve hed n e used to sertin perfusion ompromise even efore the presene of linilly visile signs. Inorportion of n eye trking devie tht orrets for eye movements during the snning proess nd lso oupled with follow up funtion tht leds to highly reproduile retinl perfusion mesurements will ly the foundtion of its prtil ppliility. This will eventully improve inter opertor nd inter session repetility. In the future, fster snning speeds would help otin lrger fields of view with higher resolution nd derese motion rtifts. Use of higher wve length (swept soure) monohromti light will lso enle quisition of more urte informtion of deeper strutures. SUMMARY OCTA is n evolving field; however, the ft tht it n detet flow ompromise, prior to the pperne of linilly meningful hnges is intriguing. OCTA will lso e dvntgeous in improving ptient re y deresing disese moridity through erlier detetion nd intervention. Further studies re required in lrger ohorts to estlish the possile ssoition etween retinl flow ompromise nd its ering on retinl pthologies. Future innovtions in oth hrdwre nd softwre tehnologies re expeted to id in the ssessment of horioretinl diseses in more detil. Finnil Support nd Sponsorship Nil. Conflits of Interest There re no onflits of interest. REFERENCES 1. Grover S, Murthy RK, Brr VS, Chlm KV. Normtive dt for mulr thikness y high definition spetrl domin optil oherene tomogrphy (spetrlis). Am J Ophthlmol 2009;148: Spide RF, Klnnik JM Jr., Cooney MJ. Retinl vsulr lyers imged y fluoresein ngiogrphy nd optil oherene tomogrphy ngiogrphy. JAMA Ophthlmol 2015;133: Ji Y, Tn O, Tokyer J, Potsid B, Wng Y, Liu JJ, et l. Split spetrum mplitude deorreltion ngiogrphy with optil oherene tomogrphy. 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