Mnflern _
`Pharmaceullcs
`Ffllll'ill Editinn, HEHiSEfl and Elllflllllflll
`
`Edited by
`Gilbert 3. Banker
`
`UniversIIy a! Inwa
`
`Iuwa my. Iuwa
`
`Christupher T. Rhodes
`Univfirfifly of Hhade Mend
`
`Hamster], Hhade fsj'and
`
`HHIILt|
`
`fl htatu'ul Imam-H. EH1.
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`i'lll'?‘
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`NI-tu. YURI:
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`. 3.4.551.
`
`LUPIN EX 1066
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`JHH-‘i: U-H=474Ffi7+li
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`Tlllh- ':‘:-:'-I‘.'-L I":
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`;'-I I:|l::L| um .1L'Ill firm-u pillmr
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`llHIIIqIIuntn
`|Iu..
`Hum-l l'rckkur.
`“H1
`"r'-.'-I'L
`I'M-:0.
`2.7” .'~1:-.I.|I:-.I.'l2|
`'I'I'I'L'JELIL.
`ml. 31:--!:-":'!'-'§"LIII.‘: I'm. Til? hH‘h-Jlfi-ill
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`||ll|'=n
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`Finn-Wm llrmilipru'rr Illiytrihu'riml
`VI .II'-'.'-:1 lick‘m: .-'I.I'.'r
`
`|1.;|-=I:|_ hwnacrlunj
`'I'I'.ll'__-':l.':.51." -'-. PLWIIIILLI: H ll. [-'H: JIiIIIII
`I.I:| 4|-l'-|-1|'u|-h-Lh.l: I'M 1' hI-Jfil-Hfih
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`'“III'M “Ml: VII-(“h
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`I'I||[‘-'. _"-'-'-'-'-'.
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`lli'klrch-cczult:
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`-.-I'-.]L'In:-:‘.
`Il'lih- hunk l.'«.|'II.‘I'I
`-"-|I|':r:\.' dlfi:l:'-ll‘1|5 -‘IZI
`iilll'lll'fillt‘l
`II‘I:
`I'I'.‘1"-.;-.-.:|-|1:_I_l "r1.1l'k:lin'__‘ 3': L11: _:|-:":1I.IL'_'.I.II'.L'I'- :llllllu‘n :-."".‘1CI‘I.'L
`
`ll'l Thu”. L|I1:I:IIIII¢~. FIII mun- |nh1r|1::|l_'_:||:-. wrung Lu;- Exgaul
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`fill-:3
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`IIHII II}. “urn-I lltklu'r. Inc. All Rights Rm-ncd.
`.
`['um'rlazlll
`l'!;_._'[|§:l|1'..;.[-___
`illll. 1'I-.';Ir|.'_ L'Irrlnll'qn.‘ I'I
`I1;-
`hu'l'lcr 'l'i~ I'm-1H r--:r .IT-jn'
`|.‘.Ir'. ELI:-
`I'n: I":|'Ir-.h:iu-_'h1 I.:I
`liilllnI'I'IIIEI.-:1 'll .ll.:r' fulfil ”I
`illi'Il'llilll'IE F'!II'.-I|.'n.2l|‘-:.".lu_.'. I'I'.-|L'I'I.'I‘:i|:'.ll.'ly. ELI-IE lL'LliIl-C'jllLI'
`I'I I11.
`:Lm Elliflfll'ulr'lli' Hung-1r inn! mint-ml -i_1.'~a:|_-|'.'_ 1'.
`|'_|'.u|..-|_ rurnnismn m
`urlllng 'r-"lT 1h: |'-'.||'-'Li-j!::.-
`
`l'Lliiui'l|1Iil'.l.'I|_.'J.||~ln:||:__':|_l'
`|-;'--i.~!.'r;-'..l."'|
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`I‘RIHT'I‘ZI) 1" ['HI: I WI] El} Er 10.1 [IE-u U]- EMI-IHH 3!.
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`-llfl
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`Lulu 1-‘I «J.
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`fig. 1
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`Turn-nu 5|i1-|.|1'n|1 hLDrIIwT-L‘rscuix
`
`Hfihjnd [he rclalli'sL-J} firnighuhrwum mmpmfijliunul
`namre ul' uplnhulmiu aulunnm, warmmium.
`and
`mntmm15. Emu-rm.
`Ije many -.1J'
`lI'II: 5mm: physica-
`chmnical nurnmuE-zrs that ufTEL'L drug gluhlllty.
`rank-13:.
`and uni-mu}. aw they: L111: I'ur ITII'HI: Llllit'l' drug prmJEm-n
`Hm :Iddllinnully. Hpm'iilljltd dosage I'nrms pram“ IIH:
`nphlhnfnua: mud-nu: dcsigncu wnh sac-me extrumllinury
`Cumprlailicmnl
`:Ind rn.|nuJ':m.:1unug uhullcngus. Thu-5::
`
`rung: fl'um unnu-rns i'm' alum-Hit; null mnsimnuy 01'
`pzlrmu-rruI-u'pe uphthnlmiu mlutiuns I'nr mmlnrulm'.
`HLII‘lEI-‘lfifi. :Lnd rt‘lrfi-hulhar use. 1:1 rususmnduhfliu ul'
`such inwluhtc suluélunurs .u. dczmnmhumnn m' Elunr-
`mncmulnnc. m mummtilminm L'lfiiitlin}! 11:: [I'm pnrjcm
`-.l|l uppnrnltlg mm-emmnal wlutinn for cmnpnhndn
`huEJ'l
`ii":- JL'Cl‘r'ICI'ILHhIl-L' uhluriLI: :Iruzl cpmtphnne bitur—
`mule. whnfir: shrlF 'rlfn: dcpcml-i un smug: mmlilmnh.
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`Uphflullulc ihmnmlhnl I'm
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`41'.‘
`
`r—UK
`III
`
`.
`
`Thnrm-naar Gun-3i
`
`CmrFlaw lulu r ruur
`
`Fruuurl 'lrnmduur
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`
`
`filEulr-cqn Pump
`
`Specular MIUEIHH
`
`'hfi'ullf Bull!
`
`Fig. I
`
`Specular mint-imp: scum [M m mill-u uncluuliun nl' uch-cl ur Llrugn ul: mill-.11 tifinuu.
`
`In linrmulnic Wllll mn-
`th: cllnilcng;
`Mun: rh‘umly.
`iJSI-cnlcy highly [Jul-BILL ilfllWE [JIL‘llL'fll
`in. diminishingly
`lnw tnnixnlruliunn ramcd ll'l'E h'nr 1'ch lnrrnuln’rmm.
`
`I'm-
`Ill-Ulcer.
`.lllNl'l-Il‘r aignlllcant nnlch. Prnccdurcs nnll
`:‘ccl'c
`inlravilrcnl
`lmplnmnliun L'Il' wall-Lined untivlrnl
`mtdiL'uLlun lmw: Erma-n l'rum th: advent nl' nrw
`Ihcrnpics l'nr -l
`|iI1:- and tyc—thrcmcmng new I'll-sense.
`HIV-£1135
`
`L'Llu: must UIILE‘L‘ prnducls in [hL' medical nn'nn—
`mcniurium. L'll'lhl‘hfllmll.‘ pchcluclfi an: ELIchnllj' undir-
`gnlng rrprr'mlsurl'un New mndcs 0|"dclil-lcring 3: drug :1}
`tin: cye url: bring acm-cly crcplcnrcd. ranging l'rum sulld.
`hydmpl'luhlc. ur hydmphilic due-dun. 1th un: instricd
`into this nphlhnlmic L'ul-llbsnuc. In convcnlinnnlly :Ip-
`plied dnsagn l'nrms :lnu. run-mg 1n Inc-ll I'nrmulnciun
`charnclcn'xlics- murlcccll} inCrcanc Ll'n:
`cflrLu':I rnnldcnc:
`
`rim: in film I'nmix cal" lhl: :31". lhcmhy pcm'ldlng drug
`1'nT nhanrplinm 1hr prnln lag-rd penndn nncl inducing the
`Frequency llhll:
`u given drug pmclucl musl
`hr: ud-
`minirchrcd. InlcnnucljaEu Elfin-cur: these:lltcn1;4.liw:5. in
`
`hnrh Ihmr physical 51m: and ct'l'ccl c-n dnrnnnn. cum
`FQE-j‘lllllfil'r'fi p-crlymnnc sync-m5 that undeJ-gn trnnaitinns
`l'wrn liquid [u gel ur Eualifiulid [1-7]-
`In as much .15 prnliucln 1hr Th: dangnnsin and
`lrc-alTnum Di ncnlnr clincnllc cncnr
`the nrl-cfll‘um cul'
`nrncuicully all Llclsagc forms»: and. [hut-L rnqulrc [hc namc-
`rrhnrrnnccuh'cul. attracts. fur their (Inclinpmcm. in lil'llfi
`Chapter wc' disculfi ll'H: :ntlrc icnpc crl' mnnidcrntlnna
`inmhml in the cch-nlnrlmam cul' uphflmimic pruducL-c
`flinging l'rcIm rcguLulury and :nmg'rtndinl ch uircmcnlfi.
`Lhmugh phyaicrrChcml-ral. safety. nncl cfllcacy cun-
`alclccniinns. In a discusslnn nl' 13w: cul' dun-age I'm-rm:
`currcnlly uni-d lag.- 1l'l.|: mtdiull: pruculinntn
`The final cnnnidcmtinn. but by nu mcani :L mincrl'
`unc.
`is me cllzslgn and wnlunflnn cll' cunluct Inns cure
`Pl'L‘IL‘lHL‘Ih- which urn: mguiultd by [he LLS. Fund and
`Drup Aclminintruucm IFDAI .15 mcclicnl dnviucn eunuc-
`
`fun the nail: and
`[they l.'ll"l.' lance-sacral muduc-n. nncnas-nrj.
`:[l'cct'iw us»: all cnntuct l.1'.‘l'l5-I:H In carrcct vinunl acuity.
`
`'l'hcs-z‘ prnclncis mcluclc l'nrmulnllnna l'nr rinsmg. smur-
`mg. cleaning.
`.Lnd disinfecting cunincl
`lrusec Willl
`nmciuliard cumwslliunfi fur c'flch muinr tyrn: cal' lcn:
`mun-Hull. LL.
`l'nard. snt'l hydrnphili-C.
`:Incl
`rugn‘l Enti-
`ncnnvmhle Inn-sum Man. lcni can: products fnr unc in
`film C‘jl: us Cumflnt drups while Mfll'lng t‘uJ-ELIJLZL lemma
`have hum deutlnpu-cl
`l'mm similar pruducts using lu-
`hricnling pnlzrrncr-l
`l'nr Imntmcnl n!" mmnl' cm: imm—
`iinn and 1-51: dullclcncy ldl'j' 131ml. The phallmuitutlull
`sac-mull drug-ling lunli run: pmclucln .InIJ. Imprm'rtl
`nTrl'IrhnlrnIc drug illusngc 1'nrn1-‘l hen-I: Intcn clEh-‘u'mlllflL'
`cul' advances in polymer nncl binmnlcrinl mien-:25 n5 is
`uvidunl in Ill-l: l'IJIIL‘nxl'Iraf:r :fltiuns.
`
`ll. HISTORICAL HAFKURUIJNH
`
`.‘I phyfiicmn TIIETFFIFIHCIll n rnnjnr npm'nncm un .I.
`"II'
`naignlcul
`In nnhlnmnnj With n hrmma lunccl: nncl
`Inn:
`buwd Elle: Rjgniur': life. 1H." ht upcncd III: by: mlutl -::Il
`
`Iii:
`and h.L‘| named
`laurel
`ntigninr with u l'I-rnn'nt
`wignmr's c513.
`l1: shall
`rcccsw: rm shckclfi ul' nilL'nL'."
`Hut
`if she I1]'I}'5]L"lfill
`in in dc-lng "ll-.15: wufilfld Inc
`
`:JT hm. dnlruycd ll]: nflgnlur'a 1:'_I.'L'_
`migniur'a Ilculh.
`113:1.“ shall c111 I'JIT hi}: hand." In: Fawn-mug L'xccn'lls 5m:
`Ham 2 cul' Ill: inn-2»: nl' Hing Humnlnmbi's ['ncle- cn-
`ng'L'c-J uhuul:
`lllIlJ ILL'. in .J bllJ-L‘l». uF flulilhh-EIJ blank Lg-
`nmul: 31ml: ahnul 2.7 m high. nnw pennancnlly
`prcacncd n: 1hc Lnnwr: Ell].
`Munliun i5. I'.l'.ld.lJ.L' ul'll'I-c' Ccldc' ul' I'Enrl'llllul'flll'lil only Lu
`plan: in human hinlnry Ihul [Ina-incl whtn rchrcncc Ln
`:31: mcdlcincs m pnulnccs was hcgmnmg m app-ear.
`Tl-n: SLllrlft'lIJl'Ji,
`in snulhurn Mennnnmmia.
`.m: can—
`fiidcml H:- l.‘IL'
`ll'IL' lerI tun rccnrd Ill'L-L'ir hintofi; hcginninp.
`
`c0111-
`nhmn HIM] HL'. TI1-c Egypnrlns niccl cuppa:
`pnunda. such mi
`ll'lul'clchll-J urnJ tl'lt'jrlillluihllu. Ln. gmcn
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`puma-.—
`__.__+..-
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`
`
`.-_t-—p.‘—-—.a-
`
`4“!
`
`eye makeup with. an tluuht. same beneficial effect
`against tnt‘eetiun. ewinn tn the antitetctet-ini ptuperties
`ul' uttppet‘ [9}. The standard wttund salt-e til" the Smith.
`Papyrus tapptesimateiy i'i't'lijt Hail—grease.
`ltuueg.r
`and lint—pruhahly sen-ct] as unr el' the earliest nint-
`ments at einttrtettt bases let the treatment nl' eye that
`east: at wuunds. The Greeks cspaadett utt IJ'tis hash:
`salve In artiste at a type-.11] chairnun tenhctrte}. a than
`fat fresh weunrls. which might have euntainea euppet.
`lead. ttr alum. in additicln tu myrrh and I't'anitirteense
`[lit] The use ef the aesthetic substance myrrh in the
`ferttt. ui stteita. hittclta. ur prubes has heart clceun-iertietl
`and attributed to the Haitians ttntl Greeks. Such sticlts
`were cstlleci saith-rte and were cltsst'tis'ed in water. Ittiiit.
`at egg white t'ut use as eyedruna. The Latin ward eni-
`it-rituu ts a den-satire at" the Greeit were. saith-rise [in
`turn tit-tired Iran-t
`i'at'h-m. a tell el' charse bread}.
`meaning a glutinuus paste math.- ftnm wheat and water
`that was relied inte thin eenes- reels. ur bleclts. Di'tea
`the physician‘s name was inscribed en these hndies
`[i I]. Ph'ney the Elcler tea. a n. 23- -'.“'t] arts-nested the. use
`siege whites tu "ce-ul" inflamed eyes. and hurt urn. rate
`at the must pepular at the plant estraets eF India. was
`reenrnmencieei especially l'ur "eye themes“ [12]
`After having placed the etigin at at ieaat twrt unease
`l'urnta tsetutiun sncl uintrnettt} i'ur treating diseraers er
`wnunels er the eye between flPPEt‘t.'IiII1J.I|.l.'i}' the first and
`secnrttl millenuitrttt Et_-r_‘.. we can reattlilsI reflect an the
`prugrers that the designers ul' dasage i'etms [at eye
`ptatluets haste matte tie-tun thrnugh the ages—until
`relatively recently.
`little er nette. fluet
`the past
`twu
`decades. heats-er. we have hugun In see new ceneepts
`emerging. same receiving the enthusiastic suppers nl'
`the uphthairnalegist and uptemetrist. whereas ethets.
`ant st: l'ertttnate- have been relegated tn the status at"
`little-used tteuetties.
`
`III. ANAHEIM? [IIF THE EYE AND ADP-l EIA
`
`Inadepth discussant. at the mutants ut' the eye and
`educate have bean adequately entrerurl elsewhere in the
`phartttaucttlttsttl literatum [I3--i'i'] unt'l itt recent letthttn
`neular nnatumy Here a htiel'us'crt-iew is presented at
`the critical ttnatuiniest features that influence the nut-
`ure atui atlrainiatratinn ui' uphthahnic nrepsrtttiuas- In
`this discusstun. eensitiertttiurt will be gl'i'tl'l ptirnariiy tu
`drugs nppiieel
`tuuieulls.
`that
`is. nntn the earnest er
`unattractive er inte the painebtal Fut'nices.
`Increas-
`ingly. drugs are being ciet'elepecl Feu- atirniaisttau'nn Its
`patentet'nl—Iype unease l'unns sulaanuutteu'vaily. httu
`Lhe anterinr and pesterinr chambers.
`the 'L-‘iirci‘luti.
`chamber. Tenen‘s capsule. ut- bj- retruhulbnr injectinn.
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`Page 6 of 66
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`Table I Astute-antral Etntetures ut' the E_t-e
`——___
`
`LanfEIuI.
`
`L‘unjuttetwa
`JHiIiEiDE Esir'lillnlrli't'ei httl.‘
`Superstar cuntunctis'ul sttc
`
`(“c-tneu
`Epithelium
`Bent-item's membrane
`Stremet i'stt bstantin prepr'tu]
`Ilesccmet's ntcnthntne
`Eraiuthelitrm
`
`Iris
`[is-int
`Fusteriur elutnthct'
`Ennules u |' firm
`Lena
`1t'itienus auteur
`
`Tennn's capsule
`Retina
`[‘iliars' heel}.- [eurte]
`Meihrtrnialt gland:
`
`Anterinr chanther
`Angie er' anteriei' chamber
`Sehlemt'n‘s meal
`Ensues er fenLttna
`Retina
`—'——-—-—-—.—
`
`Fmterictr eltamher
`Vitrcntss ehttrnher
`
`Because same al' the dthsugc Farms described may he
`t'trns'tdetetl as adjunetiue tn enitthalmic surgical pre-
`eedures. these preeetiures and the cuacurttitant use at
`the thug are tin-termed in Sec. WILD. Fer erieuuttiutt.
`readers are cncnuragea tu- familiarise thethsels'cs with
`the atuitnmical structures at the eye iTahle 1]. some at
`which are shuwn tn Fig. 3-.
`the
`The eye is essentially a glebe suspended in
`t'teulttt erhit. specutlized Fri-r sight thrungh un arrangev
`meat ul‘multiple tissues that Functtuu te l'ecus. transu
`rail. and detect iaceming iight. There is a central path
`Lhat
`light.
`travels. tn the retina. with ail
`intervening
`tissues {earn-est. aqtteuus hunter. ptttt'tl. teas. and intr-
`eeus hunter] being transparent. .15. ll HLIIEDIIIIdiflg tissues
`sen-e tu neurish. sentient. anti pretect these essential
`structunts.
`
`The cat-nea campuses unis nae siath nut” Lhe enter
`surface tii‘ the eye. yet it is the first and cute hi the must
`irnp-ertant harn'ers te esternal materiais The cut-nee is
`centpusetl el' three layers ul' varying structural and
`chemical prepcrties that Farm barriers based un selu-
`bilitgr. minute and pattitianittg nrnpertiea. mnlecuLar
`wetLu-it anti genntettzt- and specific binding character
`isties. The presence and type ul' interceiluiar iurtctiens
`regulate rnnlecular titfi'usien aruuncl the ceils. whiie the
`hy‘drepht'lie er lip-uphitic characteristic at“ each inset
`cuatrnis dilTusian aeruss and slam; the cell membrane.
`The earnest Itself has nu hlnnd 't-ese'rels an :it relies ctn
`passive difl'ttsiun ul‘ nutrients i'rurn sutruurtthttg tissues
`and aqueuus humur.
`'l'he uutertnust layer. lhs: epithelium. is eurnpeseti at
`five tu setett
`layers ul' stratified epithelial eells that
`mulseurt uni}
`IIILl-a.
`[5|] pm] hi"
`the lutttl cnrtteai
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`Page 6 of 66
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`Dphlltllrm't' l-‘linrrntet'ultkul I'nrtittrtu
`
`“fill
`
`MIIEIIIJI thambHr—H“
`
`fir'terier chamber angle
`
`Career
`
`Earl-at e-l flehlemm
`
`-— Urfilt‘tflfll} hfll'filflr'it
`
`
`FIFEEHCIT [llil'fill'jt'
`
`vain
`
`Cante'eltea
`
`Traheeuler
`meme-er}
`
`
`
`Erelera
`
`Eman-
`preeees
`
`
`
`Sumenmrc llua'rtenl :tt Ierte
`|ri$
`[actual-Ell
`
`Fee—tenet chamber
`
`__'-'l_
`
`Fl]... J .Jtnetcmteel ere-s: section el' the human eye.
`
`thickness. finest] cells cl' the epithelium nte ntitcttcnlly
`active. pmt-‘itlirtg at regular supp-I5 e-I' t..'t:iiti Iu- replenish
`[ll-tree Inst
`thrcugh :ncrmtil sinughrng nr injury. The
`tight junetttms end Iipephilic etcnc-esitieu cf the epi-
`thelium eumhine ten rii'Efll
`i.1'|'l eJantilu'e barrier tlu Inuit:-
`
`eulefi entl Frtreign eul'lstu rtees thnt ere hydmphilie I'IL' rtl'
`high tueteculnt u‘cighl The tears. cempceecl cl'tnnc'trt.
`
`t]'tI.' epithe-
`i.'l.'_t.'dl'ili.l'.'
`aqueous 11m] lipid plumes- sun-1* let
`||t.trrtr litre-cent edhesittn ut' bacteria and other I'ureign
`mntert‘uls. and influence the distrihtttten ttncl ttlxiciijr' cl‘
`l'ttrejgn mttEe‘Tiitilt [IE]. Fillttil}.
`the epithelium 1':- meta-
`hniteully highly Helix-e ngins‘t seuubiuties; while pru—
`iect't't'c ttEtlitt51 term: substances. this activity may elect
`trnpnet drug iJitJfl'L'itii'tihiiil} and therapeutic unlet Sly
`ntiieuntl}: Euwmttn's memithtne herpes-eta.- the epithe-
`lium {mm the slrt'trnn. the la yer that eetmrt-rtseti ‘Hl'l'i. hi
`the cc |'|1r.':|
`
`in eflntruel tn the cpili’tciiuttt. lite li-lltll't'ltt is TE: 30%
`
`water unt‘i crimp-user] muesli-5 [JI- ettllstgen fibrils In is
`highly crcenised ttrrttzl' thh itttcrsttccs filled t'r'lTl't glu-
`cesrtthinngtycun ensued substance end at scattering cf
`kEFutflCylfi. Net junctitttts are prestfnt. yet Lite hydrtt-
`TIht'lic flelfllt'Hl‘iIIIH-I'I presents :t stguificttnl hen-ice tr- I-i-
`pcphilie mulecules. Tlte
`stt'ume
`is
`susceptible
`tu
`salinellinte~ and water tl'tlntent must be actively e'tZI-ntrtllied
`llJ rtrl:'t't:'l"|1 ttpnetfientictn. This: is ei primary Function ['1'
`the cntlctlteltunt. n single layer nt' hcxegcnttilyr' ur-
`rttngetl cells: separated Item the street-ct h]; Deeernet's
`memhnme Since the enrnenl endttthetinl cells have
`
`[Efidilfn' passes
`iunctietts. wank-if
`discontinue-us tight
`I'tutllt‘n ttCrussr m the eru-rttt. Tu
`hen:
`the nettle-true.
`L'ltllJinlEr this. eeilulttr i1'l'l'l rturnptt
`l'|.'|-JI:i:|'l|.:-Ji|1 prnper I13-
`drminn all the stIctruL in: tlctwc Irenspnrl cf tens. cut
`Inlc 1lte nee-eves hunter With tt-ntet- refine-int;- the tenth-
`
`tltrcuglt pnesitt: dithtsic-u. These "leaky"
`gradient
`iuueliuns tun}: prefien't
`u tit‘lttslttttt
`i‘lil..t'.'il1"lJ bf mer-
`I1‘_ct;l relinn In the strnmtt art-ti present little tJI ntt barrier
`tc drug nettetrttttcn. but are ceecul iel In the titli'uemn el'
`nutrients [mm the equeeus ltumnr into the cum-Eat. The
`enrlntheliun't has an tit-ere“. lipephilir [tut-Lire thut Iirrttts
`ctfittsten el‘ ht'tlrcpntitc melcculcs.
`iI
`is Impermnl
`tc
`Etc-it! that the ltunmu ettdnthcliuttt hats tt titted uunthet
`
`instead cums
`tuituticuilf Ilelilr'e.
`than are net
`Ui- eelis‘.
`preheating fer eeli
`Inset uni} lht'uugh mtgrutttm ant!
`hypertruphy cl' intEt't-tduttl cell-s tc cm'cr guru:
`tn lite
`luyer. Inability tc centpensetc t'ct' cell lees wttt result an
`less at l'unctinn and. eerneul npecifieuljttn. Since en-
`ticthettttl chE-s ere sensilttre lc chemical and mechanical
`
`insult. ung- cplttltnltu'te pneumatic-rt ttttu ecultl ectttect
`these cells must be carefully- eeelue‘ttetl 1'ur hieetnnnnl-
`ti'Itlttz.I
`The ect'nee is ccnnectcd tn the ltrntlus re the epeuuc
`salute, the“: tuuglt fibre-elastic capsule rlntr encloses the
`eye .itl'lti urn-cities suppttrt stud nrtiteetiurt fur the in-
`terest stt‘ucttttes. The visible rn'ctl el' the sclcrtl
`'is gen-
`flail}: referred ten are the cnnjunclh-u. The strcnttt hats
`lttctsely peeked eullngen hh-rtls with sL'nttertstl til'lrtJeytes
`and line bloc-d vessel-s etc-cpl
`in line litubel i.'|.|.'l'.:l'l. Nn
`junettnnel. ectttpleeee are present. so the sclet'tt pteseute
`fll'lL'r'
`:3
`ItTtttTthilit: hen-jet
`tel
`fttreign meteriitls. The
`limb-us is [tell in blend t-eeeels. and str'ttten'tir nhsnrptiu-n
`cf tcptcetl'y applied drugs uccttrs here ['Il'lmfll'lijr'.
`thhln the tnteriur ef the eye- the E'ttttbnl elm L'L1n'tuins
`tlte [mite-cutter meelttt'ttrit and. eat rtnl nl' Sehlemm :11 the
`
`jenetinn cf the ins and eclet'tt. These structures ereiu.
`.‘tl.'El.1r:t'l1J."-. humttr lTL‘lll'i the anterior eiiittttEIcr. .t lunclicn
`essential tn. [ire-cent Httiei neetimuhlittn.
`inerettseei in-
`tmnculnr ntessmc. end gtnuccn‘ta 'I'itc iris.
`.1 rung c’r'
`
`Page 7 of 66
`
`Page 7 of 66
`
`

`

`T'I'I'II'I'I-lt-
`
`431!
`
`rnttsthhir tissue that reeuhttes Ittht entry lure the heel:
`of the eye threugh the pupil. is lueetcn ill [rent nt’thc
`lens .tntl physically terms the eiiisien between the
`numeric: ehemhet and the pesterier chamber. This
`structure is
`rich in tile-ed vessels which tlilete when
`espesetl 1e- seyett'
`trl'llttnls resulting in iridinl hyper-
`erutn end cdemtt The Lnner'enlitttt til the ins presides
`the means by which the pt'eetitjuner L'iltl centred pit-
`piilury dilatien.
`The lens is essentinlly u flettcnerl sphere thitt ts held in
`plate end cnnneetetl
`tn the eiliery hncly hy filler-like
`strands.
`the eenules el' Einn. Crimpesed el' crmccntrie
`ileyers el'erystelttne fibers. the tit-secular lens has it single
`Inyer el' epithelial cells en the tlnlefielt' sut'lhee end is
`surrcum'lccl by :1 1hin hut thug: capsule thut cenrenientty
`prflt'ttfcs the suppt'tl'l. l'et' eh ictLrtIttenlur lens tlt‘lLt erice e
`cetttrttctees lens lttts been ten-teem. The lens epiLhelisl
`cells hete seme mitetie lien-titty- :tnd hitter cells preps-cs-
`sit-rely lese their cellular eerttents and Inlet-etc tn farm the
`crystttllinel'thers. The lens is tleitihte end chenges shape in
`order In ecljust
`I'fleul
`length For
`ttettr objects tuctxtrnv
`ntetisttient. en ehility that is leet with age It rs impnnrtnnt
`tn uete that there is httteesehenge et‘metet-iets in the lens
`nncl ne less t'tl'eeJJs sci thet ell-tn; eccrrrnulutttin sheeld be
`intestiyeted Fer ephthnhnic prepsrntiens fltet .itn: eh-
`serherl
`inter the eye. The eiliury belly hes 1W“- mnjer
`Functiens. The cihttry muscle cenneets Let the settelcetul
`Ellttt and ennttel-s leret
`:teentttrne-tletien. The untennr
`pertitt-n til" the eilziitry hetdy liming the mstetlur chttml'tet'
`pmdueee the equceus hemer thttt eireulutes incress and
`lltrettgh the pure! ten the entenerrhernhcr still cut til the
`eye fur it it'tntiltustl lutmeer ul' fluid.
`
`Behind the lens is the yitreeus elttrmher that cen-
`teins 1eitrceess httmttt'- e transpareiit gelatinens ntuterinl
`1hht has me turneyer and is in direct centuet with the
`retina. The reljne is. e hileyercd hlghly metehelleully
`ect'rte tissue that trunst'errns light In em electrical sig-
`rtttl. which is processed and transmitted as electrnnic
`lrnitgcs let
`the hrttin The trssuc ts crimpnsett
`til at
`enmples utmnycment ul' phetnrccepter cells [reds and
`canes} evet'lylng the retinal pigmented epithelium
`[RPE]: end is
`isclntcrl
`t'rmu t-sscnler fluids by the
`blend-retinal hen-in: r. ti eemhinntinn etl'endetheiial eeli
`tight jut-teeters lining the retinttl bleed vessels and tight
`junctions between the RPE cells thet restricts difi‘uslen
`Tram 1he systemic uttettluljen. The ehurttid is It highly
`veseuhttiecd ceitttgceeus tissue lying between the re
`tlntl end the selerst them the eilinry he-dy tn the nptie
`nerve. The uptic nerve eennects tn-
`the retinn ill the
`tiptic dial-t. it highly yesculsrizecl ere-e thet is susceptible
`tn n-enlcr hypertensinn and drug elt'ects. Finally. see-
`E'I't'll ecccsset'y tissues [he'lneeel nre essentiel tn rtreper
`
`Lung ct II.
`
`lune-treating tttl' tht: eye. Ten-en's ettptsule- :1 thin mern-
`hrene surrcuntllttg the selcre. sceiusees the eye frem
`Il'te surrounding seelcet fer Freedom et' mat-erminl. 'i'he
`lecrirncl end Meihemisn glut-leis preside essential test
`encl lipid cemp-enents while the eyelids assist in tear
`distrthethtn sntl pretect against mechanical injury.
`Frerrt this discussicn. the reader t.':tl'l appreciate the
`intneuey til" the eye end the care required in devising
`ephtheh-nie prephrmiens in order tn preside set'e end
`effective thetupy.
`
`W.
`
`F‘Htlt Hl'lt'Ldtl‘Cfl LIE“?!J AND
`
`THERA FEL'TIE‘S lI'JIF UPHTHA Ll'tTIC
`MEDICATIIDN
`
`it ts net the purpose cut" this test te present en in—tlepth
`tct'iew hi” the phennneeteey ut' ephthelntic drugs. Fer
`this pure-use the rend-et- is referred ttt cine til the nu-
`tl'ttttt'lutitre 1retltmetits t'lf this subject I | 9-3]. Huts-Eucn
`since this teeth; is net cemmunly centered in phennstey
`schist-ll curricula. ll hriel' treatmem is presented here.
`Fer the least part. drugs used lit the eye l'sll inte- ene nl'
`fist'etul entcgetries, including miutics. Tnydrieties {with
`er witheet cyclcplcgie .teu'cityi. eyeleplegies, ltI'III-lt'te
`flemnteteries.
`enIi-irtt'eetites
`tinctuding entihietics.
`nntirit'els.
`tint-l nntihectennlsj. entiglnueetue drugs,
`surgieet aldjlll‘lflfi. diitgnestitss. and n eittegery at times
`l'er mtscellencues uses. The intended ephthelrttie use
`will define mete precisely when drug er cnmhinitlt'err e!"
`drugs is tn he used. the tippiupriete desege farm. and
`reel: et' sdntinistretnin. Fur example. the practittenet-
`will. with lines-ledge ctl' uerrtnn eerttrernclichtidns. Ltst:
`Tri}'l.l:t'.l.il.ll|: drugs specifically fer their pupillery nn-tl
`eemmmedetit‘e eFFects. hcth in the pt'eeess el' refille-
`tinn entl
`in Lhe mnneeemenl el' Irideeyclitis. tritis. ee—
`eetutttedetisc
`esetrepin.
`ehrl
`tut-
`|.‘.|fl
`.tttrepirtc.
`herrtetrepitte. shape-Lemme.
`trupieenttde. end cycle-
`pcutehtte ill‘I: esst mptes cl' pernsynnhetherntmetic drugs
`Istssessihe myrltintie end eyeleplegic activity. whereas
`phenylephnne and epinephrine tire esnntples nF sym-
`pulhemimctie drugs pelts-erasing enly mydrictic activity.
`Drugs thel may be chnscn her use In the tttunege-
`ntent el' glsucenttt may he tepicelly applied minties,
`sech :ts pilueerpine hy'tlrcchlc-rlde er nitrate. [ethn-
`chnl. echethiephhte iedidc. er demeceriem hretuitlc:
`epinephrine predruys til-:e dipisel‘ritt hydrechleride.
`nensetectiee tl-edrenct-yic blocking ngents such as ti—
`melel tueieete end henelctl hydreehlctritle. nhtt selec-
`ttt‘e fi-edrenergte hieclttttg agents such as reecmic- er
`the mere [Intent
`ll't'riI-lhi'liuxfllfll hydteehlertcle. enm-
`pnunds dict-nit] nl' puplllery ei'l'eet; tupimlly ttdtuinis—
`tet'etl
`eerl'tente
`enhyttrhse
`inhilu'tnrs.
`'sthh
`its
`
`Page 8 of 66
`
`Page 8 of 66
`
`

`

`(Hilflflflll'lit: Phnnnlnt'llienl I'rndut'rtt
`
`4-11
`
`dureelamide nntl hnnmitlrntde; prestaglnndtn antilegs
`at the etass PUFH. sueh as tstaneptest and [reveal-est.
`
`capable [IF lettering intranet-tint pressure {It-1F] sig-
`nirtettnttg With little er rte 1nl‘lttimrnrtIe-r1.I er t'tisediln~
`Ice-y respisiise; er
`the].r may he el'allzr- aiJInttttsteted
`
`tl'utt will tuner in-
`drugs. tn present an ttsmutiL' elTect
`tianeular pressure. stteh its
`‘iU‘h. gls'eerin er slitti-
`isnstirhiite. Ull‘t'E't' thugs administered etnttt.I te lesser
`inmtnenlstr pressure are the eurhnnit; unity-titans.
`in-
`Itihiters aeeteznientide nrttl methemlnmtde. Further—
`
`I'ie eheisen tn net-terse the
`ITttt'EL'_ Ihi: tnietie drugs. mag.-
`efi'eet nF mydriatjes utter rufrneLitsn tn" during. :sttsr'gie'ai
`pteeedutes sttelt es eetttrnet rerntts'el. There Is new
`available an antitngdt'itttie drug devntti el'
`|:«tt['!«tttttir:i.I
`anti-city, duriipruttttte hydruehluritie, whirl-t
`is gaining
`imports nee In the reversal at the et-t'eet nl' mydnaties.
`Dene-titling en the teeat'tnn el' eeulttr inltttnttnatien.
`F1 speeilie etirlieusterttid in :1 speetfie desage TL‘InTI
`ITIEIj'
`he ehdsen.
`t-nr instanee. n enrllunstemid nl' htgh TH't-
`tenet'. sueh as predniselene neetttte. finer-emetlteinne.
`tteitai-taztt-iasene.
`t1:
`rimettetette. mag.-
`tie ehesen t'er
`
`infinrnmntiun nf the 11qu lruet- Further
`deep-sentinel
`treatment et‘ sueh mfittmmtttlt'llt me}.- take the Fame at
`subtenen injectieas et- ettt] tsystetnie] adntittistrelien
`nt'seleered mrlieaslernitts. depending lJt'l IJte indluutiun
`:md the dnsnge Terms. neatlsthte. Fnr inflamrn utinn eli' st
`mere superfieia] nature.
`the tester strengths el' predr
`nisnlnne tteeiutt: er the tewenputeney edrtit'ttsteruids,
`such as. hydrnenrttsnne nr metirysnne. will
`tt.sunt|::.I he
`ehesen. It is new else possible tn trntl :inflttmnttltien
`Wilt'l nunstet‘uitlul ttgellls litue dielul'etlut; Lit“ kfltflt'littt.
`drugs nnt ettpeeled tel
`leis-t.- IUP.
`Drugs used t'err Ihe treatment of neuter int'eetiett will
`generally he ehesen based en the presunnttite diag~
`nttcsis er the causative ug'cnt by the upttthalatetegist.
`
`land
`Latticinttofi eonfirrntttinrt h} mlet‘nl'tistt eullurt:
`identifieatien is t'eutitiett' eertttueteet ennettrreltlis with
`the initiatien ut' therapy. This is generally JJECESHI}
`
`lteetausi: int' tin: seventy Itnd sight-threatemng nature t'tt'
`seine types el'irtreetten Fnresnrnple. lt‘tl pttltenl has :1
`foreign hedg fledged in the eetnea ei-igiitatiug Item .1
`[sntenttstllt' ettntnminuted envirunrnent.
`the physician
`tttatr ehe-ese te begin treatment rut“ the eye. sitter Fnreign
`hmtg Mme-tat. with a single er entnhinattett alttit'itietie.
`such as gentttrnttsin1 tuhren‘tyetn. ehleramptteniettl. and
`-'t
`neetnsein-nntgrnysin
`eemhtntllinn
`Recent
`1n-
`ttudaetien et'qutttntune atttibietles like eiprnfinxtteili.
`nt'ttntttein. and nnstittttt'tein lustre expanded the physi-
`cian's eheiee nt' ttt-tttltlhle prnduets fer neuttlr tnt'ee-
`tiens. The appheatien et' these agents is wnstdeted
`unprttpntste- sinet: tut infestien with Psntdunrttntts tts'r-
`rightist“ can -:.tt:sttrtt§I a. en men :In Est—4H l'tnttrs. generally
`
`the time |T takes 1n identtl’y nn int'eetintts agent. Less.
`tulttnnating.
`Itttt
`rte tess enngereus.
`tare
`tnl‘fitiens
`unused b3..-
`t-‘itIi-L'tLL‘i staehyieeeeea] and stienteeeaeal
`nrgnnrsrns. Fnr superficial haelertut int'eetinns nt' Il'te
`eenjtlnetat-tt ttnd egEEutts. suil‘enitntittes. sueh tts sedttttn
`sutfitfictstmitdtt- are usually prescribed. as ate fellas.
`mereune retide and mild stI'tIer protein. Petsphytuet'tt:
`therapy I'et errhtihtilntitt neentiturttttm is newly unt-
`t-‘ersatty required in IJ'IE United States, with silver ni-
`trate. penietlltn E. m ergr'thrnmgein being the primary
`ttllttrtl'lli-Etltt't'flfi used. F'te- .tntl pnstsurgtesl prnphglttsis
`is beeutniag Int-rte eettunenplaee with the [sue-lantern}I et'
`stlrgteniiy tent-reeled eisiu-nt L'tTl'Lt eutnhtnutietns of anti-
`iltl'eetiees. with nnti-inflnmmatnrg agents are frequently
`used tn teduee surgiea] trauma tn the eye.
`t—tJ-T fungal and 1irtr'nl Infectittns- Il'tett: an: very tiew
`agents Ihtlt the enhthnimnlegist eitn prescnhe. These
`erganisms' 1esistanee and simitnttljt In mammalian tis-
`sue make it diflieull tu lint! etTetrtit-e and safe therapies
`1-'t‘ir Instanne.
`trimturtdlne, n selective metahntis:
`in-
`
`ttihitet. has been strewn te he ttsei'ttl against herpes
`sampler. It'irusi interliun {It [tits L'urnett. FL'JI' the lrue‘hmnu
`virus and 1sirnses that. estuseinelusinn eunjunetieittsli.e..
`TR It: {the single largest etluse ef blindness werldsi'it'leH.
`nu:- smifle anti-Hint! agent h as dense nstrated satisfaeterg
`activity.
`ttnd the teeundury bacterial :rurnit'teutiuns Lit-
`this disease are rrtttnttgetfl by eent'emtnnel antihinties.
`sueh
`as
`tett'aegieline.
`ehlet'rintphenienl.
`ttnrl
`erg-
`lhrtJn'tyL'in- The lraehutttu Uitus
`itself seems te he
`snrnetehat suneeptthle 1:: these Hntthitttitts; humr. 1111-
`ten El street-ts et'ttenlment Ilttee runes per deg :tre tequtred
`tu achieve an Silt-ii elite rate {21.23}.
`A similar situnttnn exists Fur the treatment ts!" Fungal
`hertttitis The :tnltfltrtgttl antthinlie drugs nyslntln and
`nataniyeitt hat-e been efi‘eetise Ie varying degrees in
`superficial t'u ngstt tuft-tstiun. .il-h- has-e uUppEs sulfate and
`minim sulfneetttmide |14._3'5| Fur hnth n!" these drugs
`iuhtenttetes'ss ef the tepietttty administered: drug [tire-
`tiuezes enhanced unis-tiles-
`
`tilt-tags used tts surg'tetll adjuncts art: pt'irnurily in'i-
`gating setutietts- setutlens et' ptnteetstte eneynifi.
`eiseeeiasties and nnenes entwined in museum re-
`met-eat.
`intratseulttr
`lens. Tsltteentent. viLreetumy. untj
`pt‘t‘lttthitnres ttt preserve retinn] integrity. These drugs
`are eensideied true parententl {testtge terms. the design
`ttnd et't-ttutttt'nn Irt' which ttt'e dismissed at: greater detail
`elsewhere itt 1htt§ ehnprer
`ttte
`Diagnesne drugs. suett as settitltn Ittteteseestt.
`ttdrninisttered tt't-I'l-tL—q-Jlity
`tJr inlrat-elttulsl} tt.'l uid in the
`diagnosis.
`itr' such :ttnditittnfi Jlfi. enmeal Ithrusiu-ns tsr
`uteeratien and serious rettnnnathtes. This agent
`l]t1.5
`became the must widely Ltsett diagtttlstit.‘ ugett'l
`in the
`
`Page 9 of 66
`—
`
`Page 9 of 66
`
`

`

`4.11
`
`praence efnphrhalmuiugy and uptemetry. Ruse bengal
`has alsu been used tupt'ealiy. .uJIhnngh 1a a far lesser
`degree tl'nin sediuni Iluaneaein. which is available as
`well-preserved allraline snlutruns
`in euncentralruns
`ranging frem :15 in ltiutfn [25.11]. as fluttresiicin-itn-
`pregnated ahaurlient sterile pap-er stripsllii]1 at as an-
`preser't'etl. tcrtntuaily sterilised Inll'bl'r'fllflllS injections
`in cancentrstiuus ranging fin-tn :- In 25% [29“.
`Several topically applied ideal anesthetics are reu-
`linely used by the eye care speeitthst in atriaIt-i muttne
`diagnestie nreeed urea and fur ya rinLrs relariyciy simple
`surgical preeedures such as insettten uf punetai plugs
`and surgical 'l.'!lli.li'|-|'l earrectian. The first at” these In he
`Lise-ti was catchment ueneentrutiens ranging from I
`tn
`4% Eli]. Mere ntederrt Ideal ancs1hcties. hewet‘et. such
`as tetmeaine hydreehlLit-ide and preparaeatnc hydra-
`thleride. have replaced cucainc as drugs pf chairs in
`these premieres. Fur surgical prucedures nf a mere
`cmnples nature. lidncaine hydrechleride and similar
`leeel anesthetics as ectrubulhar injectiens lla't'e hecn
`nice [3]].
`The i'nregeing necryiew has presented the nutter
`classes of ephthalmic drugs. Une udditiunttl class al'
`drugs that merits hriel' discussian includes drugs ttsed
`fer the treatment at" t'artuus dry eye syutlt'un'tes. The
`must severe ei' these. ftrrutur-rmjanrrtt'e'tis .n'r'rw. int-'talt'cii
`diminished secretien eI' mueitts. ennsisting ui‘ glyce-
`pier-tins and glycesuminnglyt-ans and their eumpleaes-
`These materials sen-e re cent the curt-teal epithelium
`with a hydruphiitc layer than unifunnly attracts water
`meleeules. resulting in eycn hydratien uf the earnest]
`surface. Diminished sccrelien nf these sul-ettances cau-
`ses dry spurts tn ties-elen an the eerrtcn. resulting lli
`eunteal dehydratiurt. which can [earl
`ta uleeratinn.
`scarring. er earneal epaeitiEs [3.1].
`iii-silent pharma-
`ceutical prnduets arc at-‘ailahle [Hypetem-s. Tears Nut-
`Ural: FetteJ that writain mueetnimettc high mnlecular
`weight pnlymers that scrye tu resurface the cnrnca
`Ienipururiiy.
`thereby preventing the eFerernentiet-ieri
`dehydratiun anti alfurding the dry eye sufferer with a
`degree ef relief pre't'in'ttsly unavailahie [Eli-ll. These
`agents are net pharmaeelug'eally aetit-e. altlteugJ-i re-
`cent research itsds tn the premise ni' drugs that will
`stimulate tear preduetiun l‘cu' lunger-term relies".
`
`it. HENERAL SAFETY CDNSmEItATItJNE
`
`it. Sterility
`
`Every nphtltuirrtte preduct must be rnanul'autureii nn-
`det eunditiens validated re render it sterile in its final
`mainline:
`fur
`the shelf life at the precinct [Jiint
`
`Langel til.
`
`Sterility testing is IL'i'l nrlttrted an each lii1 iii" npltthalrrtii:
`pruduct by suitable ptueedures as set faith in the
`apprnpriute pharrnacapcin and saltdated tn each
`manufacturer‘s luberatery. Wl'llli: Llie
`rnsjnrity ei'
`uphthalmie preparations enntain prcficfl'uli'i-lei
`fur
`l'l'lLlllIlrl-lE-LIL'IEE use. sterile preparuttens ||.'| special cen-
`lainers i'ut' individual use en a srngle patient must he
`made at-‘atlable.
`'I'lijs availability is especially etitiral
`l'ur every huspiial. uffiee. nr ether installatiun where
`accidentally er surgically traumatised eyes are treated.
`as well as tar patients intnlerant tu ptttsertltlljt'ea
`The USP recnghiaes sits methuda at" achieving a
`sterile prudact:
`Iai stcatn sterilisatiun.
`thi
`tlry~heat
`sterilisalten. {ci gas sterilisatten.
`[d] sterilisatiun hy
`iunieing t'atliatinn. rel sterilised-en by Filtrnncin. and if]
`ase