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`14446501248894944534
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`Letter to the Editer
`
`intravitreai silicone ail
`
`{Irapiets £03313ng
`pegaptanib injectien
`
`Kamal
`Melmcl &1im Kmabqra.
`"furgay Dzbéieu and Kuhn: Serefoglu
`
`Retina Unit, Vakif (Rumba Education
`and Research Hospital. Ophthalmnlegy
`Ciiaic, {smnhuL 2‘11er
`
`deli: 19$ E i Efj.l?55~3?68.2068fi133§.x
`
`Editor,
`twentiy
`injaction has
`I mmvitrcal
`gained in pogulafity fer the neat
`merit of many retinal {11335193233 i’cgap-
`tanib is ax: agent used in intravimal
`lnjectian m treat choroidal neovascu»
`iarizatifias
`by
`repeated
`injectiens
`admiaismreé every 6 weeks. Westward
`intraocmm migratian uf silicone ail
`dmglets causeli by inlravitraal pegapw
`tanib injections wag mpfirted pawl»
`ously {Fraund at al. 2605).
`We report three cases of hatravitreal
`silimne ail (impleis {gnawing pagapta-
`aih injectiox:
`for
`the :reatment 03'
`submixml chemiéal neavasmziar mem»
`branes.
`In Juiy 20m, pcgapmlib
`became the: firs: antiwascular cadothev
`lial gmwth faetor (antéy‘l/fiGF) agent
`to be apmaved far ocular use in Tusk
`key. The medication is disadhuleé in
`pmfiiled
`glass
`syringes
`containing
`0.3 mg pegaptarsib in (3.69 ml 5933:3502}.
`Of 22 eyes
`ingested intraviueaiiy
`with pegaptafiib between
`(higher
`290? sad April 2&3, mm ware
`observed to contain presumed intra»
`Vilma! silicone oil droplets. The drop-
`lets were firstly noticed msicnaiiy
`during minim: epmhalmological exam-
`ination in em: patient? eye. Conw
`quenfiy. we
`underseok
`a
`careful
`examination 0? all pegapiaaibiajmtcd
`patients and we {amid intraviml city
`draplets in {we eyes of two other
`patients. Nana of the 3233;: patients
`with.
`intravitmal oily dmpiets mm."
`plained of fimms in their
`via-ml
`fields. The intravimal dwpiets were
`small, spherical,
`translucent
`fereign
`Wins. Under biomicmscnpic exsmh
`31313931. 3133 drcplets resembled siliceae
`
`
`
`Fig. l. Slitéamg} hiemicmmpy dammstm.
`[lag three oily dfeplfils in {he wfid-vitmous
`gravity.
`
`nil remnams we}: as mass: mmmaniy
`absemed ix: the vitreotxs cavity of vit-
`recmmized eyes Foliowing siliceue oil
`removal. By mantras: with the Vilma.
`tomizad eyas,
`the droplcts Ilfi
`these
`three pazients’ eyes were embedded in
`the vitreeus gel 323d Chang“! position
`with vitreaus afierwovtments (Fig. 1}.
`These smalé oily bubbles were men:
`easily detectable 4m ecuiar echogiaphy
`(Fig. 2) because of £33133:
`3139333233313
`mggcrated cchogenicit'y
`ami
`size
`mused by the lypical ‘Rayieigh‘ scat»
`lazing of ultrasaumi from the vitre—
`auwil
`interfacc.
`as
`repaflefi
`by
`Spaide cl. 3]. (20933.
`We aged inducfiveiy coupled glama
`mass spectmmctry (ICEMS) it: hast
`
`
`
`“gt-2. 34.63:: uluasanogmphy self the 5am
`eye as in Fig. l {iamanstmm 31 lypical seal-
`baring with film hypmchogmic epacilies.
`
`for the preseme 96531353363: (53') in we:
`used and rm: unused pagapmrzilrfilled
`syringe. Endumively coupled plasma—
`- MS is a highly sensitive method
`remézzely used :0 éetmnine tram ele~
`mania. -Wc dcmenstrated the prismatic
`of Si in 3152333 and unuscé syringes and
`also in the pagaptanib saluting itself
`(Fig. 3}. These findings sugaport
`the
`hypolhfisis that oiiy inflavltmal dmpw
`less
`foiiowizag pegaptanib iajeetion
`may be silicone oil
`that originated
`From syfingfi used m injcct pcgapea-
`nib.
`Sificanization of the inner syringe
`wall and enter plunger surface serve
`tn cfecreasc frictim fer pistes] move»
`men: mad minimize protein summation
`in prolong drug smbility. Because sili~
`cane ail has a mlativeiy law whesive-s
`71:55,, it may migrate firm the syringe:
`and oeutamixzaw the drug. The release
`of silimne oil from disposable syringes
`during insulin expulsion has been
`repomxi
`to result
`from mechanical
`abrasion and flushing aetiens on the
`silicenimd plastic surfaces of the: syr‘
`Eng: banal and plunger {Ghanaian
`at 35. ESE). Aims: all ophthalmic
`viscosxirgical deviczs {GVDS} injectad
`inla the amulet chamiacr mm found
`:6 margin small mamas of siiiwne
`oil, which. is usefl as a lubricant {at
`the paefilled (ND syrixige (Olsrslmm
`e: at. 2064).
`Pfigaplanib. ranibizumah and bew
`acizumab are the current anfi-VEGF
`agznis 11566
`intravitmaliy,
`bufi haw
`aeizumab is no: approveé fm‘
`intra-
`vitrcal delivery and thus its use is
`afi’dabcl.
`Inlravimal
`injeclibn
`331‘
`VEGF inhibitors as an invasive proce~
`dure marries me risk of blinding com-
`plicatium;
`such as
`eudophthaimizis
`and minai detachmcm; maneuver,
`potential systemic slfie-effscm include
`arterial hymensicn. thrombaembolic
`Events and gastroimestinai wading
`(3% Cam“ 206?).
`
`
`
`as
`
`a:
`
`mazm
`
`"m
`
`m
`
`”—844
`
`Fig. 3. Silica: (atomic amigm Z9 gfinml} W by ma caminuaus red line (Matted if: was:
`amounts in the “gamma: wlmim lay inaaciivgly coupled plasma mass spmmmtry malys'm.
`{Other lines «It: blank}
`
`; Eingegangen
`
`
` 15.
`
`IienkelfireuerEfi'arme:
`
`
`; Amulfpark
`REGITCOO130974
`
`2385
`
`Regeneron Exhibit 1080.001
`
`

`

`sj§_26ieLO1name—00000253
`
`28.08....201‘5- 0 '1 "OOH? 7-06000‘l8‘8
`
`
`
`m— Acre. OrnrnALmoLoorcn 2010 ?
`
`In our experience with intravitreal
`bevacizumab injection over 2years.
`we have not observed a single case
`of intravitreal
`silicone oil droplets.
`Renibizumab is not yet approved or
`commercially
`available
`in Turkey
`and therefore we have no experience
`with it.
`By contrast with pegaptanib, neither
`ranibizumab nor
`bevacizurnab are
`stored in prefilled syringes. We think
`that intravitreal contamination by sili-
`cone oil droplets is most likely asmci-
`ated with the use of prelilled syringes.
`The functional and clinical conse-
`quences of
`intravitreal
`silicone oil
`droplets are unknown, but their occur-
`rence could be avoided by using new-
`generation prefilled syringes that do
`not have an internal silicone coating.
`
`Acknowledgements
`We thank Professor Ahmet Kasgoz
`from the Department of Chemical
`Engineering, University of
`Istanbul
`for
`providing
`inductively
`coupled
`plasma mass Spectrometry analysis for
`this study.
`
`Ohrstrom A, Svensson B, Tegenl'eidt S,
`Celiker C & Lignell B (2004): Silicone oil
`content in ophthalmic viseosurgieal devices.
`J Cataract Refract Surg 30: 12784280.
`Spaide RF, Chung lE & Fisher YL (2005):
`Ultrasmmd detection of silicone oil after its
`removal
`in retinal
`reatmchment surgery.
`Retina 75: 943-0945.
`
`
`
`References
`Chanlelau E, Berger M dc Béhiiten B 0986):
`Silicone oil released from disposable insulin
`Syringes, Diabetes Care 9: 672—673.
`Ia Cour M (2007): [ntravitreal VEGFJnhibi—
`tors: is Avastin a generic substitute for Lu‘
`centis? Acta Ophthalmol Scand 35: 2—4.
`Freund KB, Laud K, Eandi CM Sr Spaide
`RF {2006): Silicone oil droplets following
`intraviueal injection. Retina 26: 70l‘703.
`
`_
`Correspondence:
`M. Selim Kocabora
`Sanatcilar Sitesi
`27 E Biol: Dalre: l2
`Tarabya-Sariyer
`3445? Istanbul
`Turkey
`Tel: + 90 Zn 534 6900
`Fax: + 90 212 621 7580
`Email: kocabora@gmail.oom
`
`lllllllllllllllllllllllllElllllllllll
`
`14446501248894944514
`
`
`
`
`
`e45”
`
`REGITCOO130975
`
`Regeneron Exhibit 1080.002
`
`