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Gracfe 's Arch C lin Exp Oph thalmol (1987) 225:8%83 Graefe's Archivefor CliniCal and ExperimentalOphthalmology Springer-Verlag 1987

Age-related changes in human vitreous structure*J. Sebag**' ***Eye Research In stitute of Retina Fou ndation, and Harv ard Medical School, Boston, MA , USA

Abstract. Changes in v i t reous s t ruc ture tha t occur w i thag ing a re imp or t an t i n the pa thogenes i s o f v i t reous li que fac -t ion (synchis is senil is) , vi t reous detach men t , and re t inal dis -ease . V i t reous morphology was s tud ied in 59 human eyespos t -mor tem us ing da rk- f i e ld hor i zonta l s l i t i l l umina t ionof the ent i re dissected vi t reous . In man y individuals you nge rthan 30 yea rs, t he v i t reous was hom ogene ous in s t ruc ture .Middle -aged ind iv idua l s had macrosco pic f ibe rs in the cen-t ra l v i t reous , which coursed an te ropos te r io r ly and inse r t edinto the vi t reous base and the vi t reous cortex, pos ter iorly.During senescence, the vi t reous volume was reduced, thevi t reous body was col lapsed (syneres is ) , and the f ibers wereth ickened , t o r tuous , and su r rounded by l iqu id v i treous .Thi s s equence of age - re l a ted changes p roba bly re su l t s f roma progres s ive reorganiza t ion of the hya luron ic ac id and co l-l agen molecu la r ne tworks . Charac te r i za t ion of the molecu-lar events underlying these changes wi l l e lucidate the mech-anisms of the phen om en a o f synchisis , syneres is , and de-t achment , an d ma y prov ide me tho ds wi th which to p reventor induce v i t reous de tachmen t p rophylac t i ca l ly .

IntroductionHis to log ic s tud ies pe r formed dur ing the e igh teen th andnineteenth centuries resul ted in four di fferent theories ofv i t reous s t ruc ture : t he A lveola r Theory o f Dem ours , t heL a m e l l a r T h e o r y o f Z i n n , t h e R a d i a l S e c t o r T h e o r y o f H a n -nover , and the F ibr i ll a r Theory of Re tz ius (Sebag and Ba-lazs 1985). Recent studies by Eisner (1973 a, b, 1984), Balazs(1984), and F oo s and Whee ler (982) have form ed our cur-ren t concept s o f v i t reous s t ruc ture and the pheno men onof v i t reous de tachment . I t is know n tha t de t ac hmen t o fthe v i t reous p l ays an impor t an t ro l e in the pa thogenes i sof rhegm atogeno us re t inal de t achm ent (Schepens 1983;Chaine e t a l . 1983), mac ular- hole for ma t ion (Avi la e t a l .1983), neov ascular izat ion (Jalkh e t a l . 982; F aul bo rn a ndBow ald 985), and cys to id ma cul ar edem a in pars plani t is(Hi rok awa et a l . 1985) as wel l as , perha ps , a ph aki a (Sche-pens e t a l . 984; Sebag and Balazs 984). I t is not k now nwha t s t ruc tura l changes and under ly ing molecu la r even t s* Presented at the XVth Meeting of the Club Jules Gonin, Copen-hagen, 10-15 August 1986** Kn app Fellow of the Heed Ophthalmic Founda tion, 1985-1986*** Present address: 8th Floor Suite, 18800 Delaware Street, Hunt-ington Beach, CA 92648, USA

cause de tachment o f t he pos te r io r v i t reous. There i s , how-ever, an inc reased inc idence of pos t e r io r v i t reous de tach-ment w i th inc reas ing amou nt s o f synchi si s (O 'Mal l ey 1976;Foos and Whee le r 1982) . Fur the rmore , La rs son and Os te r -l in (1985) have show n tha t the extent o f vi t reous detach -ment inc reases w i th inc reas ing amo unt s o f l i quid v i t reous .The presen t i nves t iga t ion was an a t t empt to l ea rn moreabout v i t reous synchi s i s ( l i que fac t ion) and de tachment bys tudying the s t ruc tura l changes tha t occur in normal h um anvi t reous th roughout l i f e . The obse rva t ions document a p ro-gress ive reorg anizat io n o f the vi t reous and sugges t di rec-t ions for con t inued re sea rch in to the under ly ing molecu la revents.Materials and methodsFifty-nine eyes from 31 individuals (18 males , 13 females ;age range, 33 weeks of ges ta t ion to 94 years) were obtain edt h r o u g h t h e c o u r t e sy o f t he N e w E n g l a n d E y e B a n k a n dt h e N e w Y o r k B a n k f o r S i g ht R e s t o r a ti o n . N o n e o f th edonors had a h i s to ry of ocu la r d i sease or t r aum a , o ph-thalmic surgery, or diabetes mel l i tus .

The eyes were kep t i n moi s t chamb ers a t 4 C and wereexamined wi th in 12-24 h of donor dea ths . Spec imens wereprepa red by d i s sec t ing the s c le ra, choro id , and re t ina awayf rom the v i t reous f rom the ora s e r ra t a to the pos te r io r po le .Sutures were placed through the l imbus , and the ent i re vi t -reous ( s t i l l a t t ached to the an te r io r s egment ) was mountedon a f ram e in app roxim a te ly the in v ivo pos i t ion and thenplaced in a chamber conta in ing an i so ton ic o r ba lancedsal t solut ion.

The vi t reous was i l luminated from the s ide wi th a hori -zonta l s l i t - l amp beam and was examined f rom above . Theimage created in this way represents a horizontal opt icalsect ion through the vi t reous . The vert ical locat ion of thiss ec tion and the th i ckness o f t he i l l umina ted por t ion couldbe ad jus t ed a s des i red . Photographs were t aken in a da rkroom wi th a b l ack background us ing a 55- ram macro l ensand I l fo rd XPI-400 f i lm.

ResultsThe f indings are presented in three age categories , i .e . ,young, middle aged, and senescent . Al lowing for a certa inam oun t o f i nd iv idua l va r i ab i l it y , t he desc r ip t ions g iven be -low are representat ive for these three groups . Table I pres-ents a general ized descript ion of the obs erved chang es inv i t reous s t ruc ture tha t occur th roughout l i f e .

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90

Fig. 1. Vitreous of a 33-week-oldhuman embryo. The anter ior segmentis below, and the poster ior pole i sabove. The vi t reous i s homogeneousin s t ructure except for the vi t reouscor tex and Cloquet ' s canal , x 5.4

Fig. 2. Vitreous of a 6-year-oldhuman. The anter ior segment i sbelow, and the poster ior pole i sabove. No macroscopic s t ructures arevisible within the vitreous except forremnants o f C loquet ' s canal , x 4

Fig. 3. Vitreous of a 59-year-oldhuman. Only the cent ra l andposter ior v i t reous are shown, wi th theposter ior pole above. Fine , para l le l ,l inear f ibers course anteroposter ior lyin the central vitreous, these beingsurrounded by less dense light-scat ter ing media (Sebag and Balazs1985). x 8.3

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91

Fig. 4. Special dissection of a humanvitreous. The sclera, choroid, andretina surrounding the optic nervewere left attached to the vitreous,while these layers were dissected fromthe peripheral, equatorial, andretroequatorial vitreous. There wasno extrusion of vitreous into theretrohyaloid space. Macroscopiclinear fibers course anteropo steriorlyand are oriented toward the macula.x2 .9

Fig. 5. Vitreous of an 88-year-oldhuman. The anterior segment isbelow, and the po sterior pole isabove. The size of the vitreous isreduced, and the shape is collapsed,as evidenced by the irregular contou rof the vitreous cortex. Fibers arepresent throughout the vitreous. Thefibers are thickened, tortuous, andintertwined. Adjacent to the fibers,there are spaces devoid of anystructure (Sebag and Balazs 1985).2.7

Young (perinatal to 29 years o f age)Tw e n ty - th re e e y e s f ro m 1 2 d o n o rs i n t h i s a g e r a n g e w e ree x a m i n e d ; 1 8 o f t he e y e s w e r e o b t a i n e d f r o m d o n o r s a g e d1 4 y e a r s o r le s s. T h e v i t r e o u s e x h i b i t e d a r e m a r k a b l y h o m o -g e n e o u s a p p e a r a n c e . T h e o n l y d i s c e rn i b l e st r u c t u r es w e r eth e v i t r e o u s c o r t e x a n d , i n y o u n g e r i n d iv id u a l s , a d i s t i n c tc a n a l o f C l o q u e t ( F i g . 1). D u r i n g c h i l d h o o d , t h i s c a n a l b e -c a me l e ss p ro min e n t , a l t h o u g h s t i l l v i s ib l e. In 1 5 o f t h e1 8 e y e s f ro m d o n o rs a g e d 1 4 y e a r s o r l e ss , n o p ro min e n tf ib ro u s s t ru c tu re s w e re p re se n t w i th in t h e v i t r e o u s (F ig . 2 ) .Adult (30-69 years of age)Tw e n ty - th re e e y e s f ro m 1 2 in d iv id u a l s in t h i s a g e g ro u pw e re e x a min e d . Th e re w e re su b s t a n t i a l d i f f e re n c e s i n c o rn -

p a r i s o n t o t h e f i n d i n g s f o r t h e v i t r e o u s o f y o u n g i n d i v i d u a l s .W i t h i n t h e c e n t r a l v i t r e o u s , t h e r e w e r e m a c r o s c o p i c , l i n e a rf i b er s o r i e n t e d a n t e r o p o s t e r i o r l y ( F i g. 3 ). A n t e r i o r l y , t h ef i b e r s i n s e r t e d i n t o t h e v i t r e o u s b a s e , b o t h a n t e r i o r a n dp o s t e r io r t o t h e o ra se r ra t a (Se b a g e t a l . 1 98 7 ). Th e re w a sa d i s t i n c t c u r v i l i n e a r o r ' a n t e r i o r l o o p ' c o n f i g u r a t i o n t oth e f i b e r s i n se r t i n g a n t e r io r t o t h e o ra se r ra t a . In t h e p o s t e r i -o r v i t r e o u s , m o s t f i b e r s w e r e o r i e n t e d t o w a r d t h e m a c u l a ,a n d a f e w in se r t e d in to t h e p re ma c u la r v i t r e o u s c o r t e x (Se -b a g a n d Ba la z s 1 9 8 4) . Ra i s in g o r l o w e r in g th e l e ve l o f t h eh o r i z o n t a l p l a n e o f t h e s li t i l l u m i n a t i o n b e a m d i d n o t g i v et h e i m p r e s s i o n t h a t t h e s e s t r u c tu r e s w e r e v e r t i c a l m e m -b r a n e s b e i n g i l l u m i n a t e d i n h o r i z o n t a l c r o s s - s e c t io n . R a t h -e r , d i f f e re n t f i b e r s w e re se e n a t d i f f e re n t l e v e l s i n t h e c e n t ra lv i t r e o u s .

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92Table 1. Human vitreous structure throughout l ifeAge Num ber Observat ionsrange of(years) eyes Fibers Liquefaction Others

0- 9 12 None None C l oque t 'scanal10-19 8 Occasional No ne Cloquet ' s canal(occasional)20-39 8 Early fibers Slight Cloq uet 's canalcentral (one case)changes40-59 18 Prominent , Hon eycom b Onset of PVDparallel pocketsnear cortex60-79 5 Prom inent; Present Increasingat t imes, near cortex incidence ofirregular and centrally PVD80-99 8 Thickened, Prom inent Reducedtortuou s, near cortex vitreousno longer and centrally vo lum e;parallel collapsed PVD(syneresis)PVD = Poster ior Vit reous D etachme nt

T h e p o s s i b i l i t y t h a t t h e s e f i b e r s r e s u l t e d f r o m s a g i t t a l( a n t e r o p o s t e r i o r ) t r a c t i o n o n t h e c e n t r a l v i t re o u s b y p o s t e r i -o r v i t r e o u s e x t r u s i o n t h r o u g h t h e t w o ' h o l e s ' i n t h e p o s t e r i -o r v i t r e o u s c o r t e x ( S e b a g a n d B a l a z s 1 9 84 ) w a s i n v e s t i g a t e di n s p e c i a l p r e p a r a t i o n s . I n 3 e y e s , t h e s c l e r a , c h o r o i d , a n dr e t i n a w e r e l e f t a t t a c h e d t o t h e p o s t e r i o r v i t r e o u s . T h e r e -s u l ts d e m o n s t r a t e d t h a t , e v e n in t h e a b s e n c e o f a n y p o s t e r i -o r v i t r e o u s e x t r u s i o n , t h e r e w e r e l i n e a r f i b e r s c o u r s i n g a n -t e r o p o s t e r io r l y a n d o r i e n te d t o w a r d t h e m a c u l a ( F ig . 4 ).

Senescent (over 70 years of age)T h e 1 3 e y e s i n t h is a g e g r o u p s h o w e d d e g e n e r a t i o n i n t h ev i t r e o u s s t r u c t u r e . F i g u r e 5 i l lu s t r a t e s t h e m o s t a d v a n c e dc a s e o f d e g e n e r a t i o n . T h e v i t r e o u s s iz e w a s r e d u c e d , a n dt h e o v e r a l l s h a p e w a s c o l l a p s e d , a s e v i d e n c e d b y t h e i r r e g u -l a r c o n t o u r o f t h e v i tr e o u s c o r t e x . F i b e r s w e r e n o l o n g e ro n l y p r e s e n t i n t h e c e n t r a l v i t r e o u s , b u t w e r e d i s t r i b u t e dt h r o u g h o u t t h e v i tr e o u s . T h e f i b e r s w e r e n o t f i n e , s t r a i g h ta n d g r o u p e d i n p a r a l l e l b u n d l e s , b u t w e r e t h i c k e n e d a n dt o r t u o u s . A d j a c e n t t o t h e d e g e n e r a t e d f i b e r s , t h e r e w e r es p a c e s t h a t c o n t a i n e d l i q u i d v i t r e o u s . I n t h e s u b c o r t i c a l r e -g i o n ( a n t e r i o r t o t h e v i t r e o u s c o r t e x ) , t h e s e s p a c e s w e r el a r g e r a n d c o r r e s p o n d e d t o ' l a c u n a e ' .D i s c u s s i o nT h e r e a r e f o u r m a j o r d i f f i c u l t i e s i n h e r e n t i n t h e s t u d y o fv i t r e o u s s t r u c t u r e : a r t i f a c t s th a t r e s u l t f r o m t h e u s e o f h i s t o -l o g i c t i ss u e f i x a t iv e s ; t h e a b s e n c e o f i n t r a v i t r e a l l a n d m a r k st h a t r e s u l t s i n l o s s o f o r i e n t a t i o n w h e n t h e v i t r e o u s i s r e -m o v e d f r o m t h e e y e ; d i s t o rt i o n o f th e s h a p e o f th e v i t r e o u sw h e n e x a m i n e d i n v i tr o ; a n d t h e t r a n s p a r e n c y o f th e v i tr e -o u s w h e n v i e w e d u n d e r d i f f u s e l i g h t . I n t h e p r e s e n t s t u d y ,t h e s e d i f f i c u l t i e s w e r e a v o i d e d a s f o l l o w s : b y e x a m i n i n gf r e s h , u n f i x e d s p e c i m e n s ; b y l e a v i n g t h e v i t r e o u s a t t a c h e dt o t h e a n t e r i o r s e g m e n t a n d m o u n t i n g t h e s p e c i m e n i n t h ei n v i v o p o s i t i o n ; b y i m m e r s i n g t h e s p e c i m e n i n s o l u t i o nt o m i n i m i z e s h a p e d i s t o r ti o n ; a n d b y e x a m i n i n g t h e v i t re o u s

w i t h d a r k - f i e l d s l i t i l l u m i n a t i o n u s i n g a n i l l u m i n a t i o n - o b -s e r v a t i o n a n g l e o f 9 0 , w h i c h m a x i m i z e s t h e T y n d a l l e f f e c t( E i sne r 1984) .T h i s a p p r o a c h e n a b l e s e f fe c ti v e v i s u a li z a ti o n o f h u m a nv i t r e o u s s t r u c t u r e . T h e r e s u l ts o f th e p r e s e n t s t u d y d o c u -m e n t p r o g r e s s i v e c h a n g e s i n n o r m a l v i t r e o u s t h r o u g h o u tl if e. T h e p r e s e n c e o f a h o m o g e n e o u s s t r u c t u r e d u r i n g c h i l d -h o o d i s c o n s i s te n t w i t h t h e p r e d o m i n a n t l y g e l s t a te o f t hev i t r e o u s i n y o u t h ( B a l a z s a n d F l o o d 1 9 78 ). T h i s g el v i t r e o u sc o n t a i n s t h i n f i b r il s o f a s p e c i al t y p e - I I c o l l a g e n o r g a n i z e di n a r a n d o m n e t w o r k ( S n o w d e n a n d S w a r m 1 9 8 0 ) . T h e f i -b r i l s a r e s e p a r a t e d b y l a r g e m o l e c u l e s o f h y a l u r o n i c a c i dt ha t s t ab i l i ze t he ge l s t a t e ( F es s l e r 19 60 ; Ba l azs 1961 ; S no w-d e n 1 9 82 ). T h i s a r r a n g e m e n t p r e v e n t s c r o s s l in k i n g o f c o l la -g e n f i la m e n t s , m i n i m i z e s l i g h t s c a t t e ri n g , a n d m a i n t a i n s t h eo p t i c a l t r a n s p a r e n c y o f t h e v i tr e o u s . I n a d u l t s , m a c r o s c o p i cf i b e r s fi r s t a p p e a r i n t h e c e n t r a l v i t r e o u s . S e b a g e t a l . ( 1 98 7 )h a v e s h o w n , u s i n g t r a n s m i s s i o n e l e c t r o n m i c r o s c o p y , t h a tt h e se f i b e rs a r e c o m p o s e d o f p a c k e d b u n d l e s o f p a ra l le lco l l agen f i b r i ls .T h e p r o c e s s o f fi b e r f o r m a t i o n o c c u r s a t a b o u t t h e s a m ea g e a s th e o n s e t o f v i tr e o u s l i q u e f a c t i o n ( B a l a z s a n d F l o o d1 9 78 ) a n d a t t h e s a m e l o c a t i o n a s t h e e a r l ie s t m a n i f e s t a t i o n sof l i que f ac t i o n , i . e ., t he cen t r a l v i t r eou s ( E i sne r 1973 a , b ) .T h e r e f o r e , b o t h s y n ch i si s a n d f i b e r f o r m a t i o n p r o b a b l y r e -s u l t f r o m t h e s a m e u n d e r l y i n g m o l e c u l a r e v e n t s . D u r i n go l d a g e , t h e v i tr e o u s v o l u m e is r e d u c e d a n d t h e s h a p e i sc o l l a p s e d . T h e f i b e r s d e g e n e r a t e a n d a r e l o c a t e d a d j a c e n tt o l a c u n a e o f th e l i q u i d v i tr e o u s . T h e s e o b s e r v a t i o n s a r ec o n s i s t e n t w i t h t h e f i n d i n g o f B a l a z s a n d F l o o d ( 1 9 7 8) t h a t ,b y t h e a g e o f 8 0 - 9 0 y e a r s , o n e - h a l f o f t h e v i t r e o u s i s ina l i q u i d s t a t e . T h i s p r o b a b l y r e p r e s e n t s t h e a d v a n c e d s t a g eo f a m o l e c u l a r r e a r r a n g e m e n t t h a t b e g i n s d u r i n g y o u t h a n da c c e l e r a t e s d u r i n g t h e f i f t h a n d s i x th d e c a d e s o f li fe .I t i s l i k e l y t h a t s o m e a l t e r a t i o n i n t h e c o l l a g e n / h y a l u r -o n i c a c i d c o m p l e x r e s u l t s s i m u l t a n e o u s l y i n v i t r e o u s s y n -c h i s i s a n d f i b e r f o r m a t i o n . A l t h o u g h t h e r e i s , a t p r e s e n t ,n o e v i d e n c e f o r th e e x i s te n c e o f a n a c t u a l c h e m i c a l b o n db e t w e e n h y a l u r o n i c a c i d a n d c o l l a g e n ( B a l a z s 1 9 8 4 ) , i t h a sb e e n s u g g e s t e d t h a t s u l f a t e d g l y c o s a m i n o g l y c a n s a c t a s a' g l u e ' b e t w e e n h y a l u r o n a t e m o l e c u l e s a n d c o l l a g e n ( A s a k -u r a 1 9 85 ). A m o r e e s t a b l i s h e d i n t e r a c t i o n o c c u r s o n a p h y s i -c o c h e m i c a l l e v e l , w i t h h y a l u r o n i c a c i d b e i n g ' b o u n d ' t oc o l l a g e n b y e l e c tr o s t a t i c fo r c e s ( C o m p e r a n d L a u r e n t 1 9 78 ).G e l m a n a n d B l a c kw e l l (1 9 7 4) h a v e s h o w n t h a t t h i s c h a rg ei n t e r a c ti o n c a n i n f lu e n c e t h e c o n f o r m a t i o n a l s t a te o f p r o -te ins .T h e " e x c l u d e d v o l u m e e f f e c t " ( O g s t o n a n d P h e l p s 1 96 1)a l so i n f lu e n c e s t h e c o n f o r m a t i o n a l s t a te o f th e s e m a c r o m o l -e c u le s b y f a v o r in g m o r e c o m p a c t t e r t ia r y a n d q u a t e r n a r ys t r u c t u r e s ( C o m p e r a n d L a u r e n t 1 9 7 8) . T h u s , c h a n g e s i nt h e p h y s i o c h e m i c a l i n t e r a c t i o n s b e t w e e n h y a l u r o n i c a c i da n d c o l l a g e n m a y b e t h e i n i t i a t i n g e v e n t s t h a t l e a d t o t h es t r u c t u r a l c h a n g e s o b s e r v e d in t h e p r e s e n t s t u d y . E v i d e n c ei n s u p p o r t o f th i s h y p o t h e s i s c a n b e f o u n d i n r e c e n t w o r k( A r m a n d a n d C h a k r a b a r t i 1 98 7) d e m o n s t r a t i n g c o n f o r m a -t i o n a l d i f f e r e n c e s b e t w e e n t h e h y a l u r o n i c a c i d m o l e c u l e sp r e s e n t i n l i q u i d v i t r e o u s a n d t h o s e l o c a t e d i n g e l v i t r e o u s .F u r t h e r w o r k m u s t b e u n d e r t a k e n t o i d e n ti f y t h e e x a c t n a -t u r e o f t h e h y a l u r o n i c - a c i d / c o l l a g e n i n t e r a c t i o n o c c u r r i n gi n t h e v i t r e o u s a s w e l l a s i n o t h e r c o n n e c t i v e t i s s u e s a n de x t r a c e l l u l a r m a t r i c e s . A b e t t e r u n d e r s t a n d i n g o f th i s i n te r -a c t i o n a n d t h e c h a n g e s t h a t o c c u r d u r i n g s y n c h i s i s s e n i l i sa n d v i t r e o u s d e t a c h m e n t c o u l d r e s u l t i n t h e d e v e l o p m e n t

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93of prophylactic therapeutic inter vention s intend ed either toinduce or to inhib it liquefaction and vitreous detachment ,dependi ng upon the clinical circumstances.

Acknowledgements. I am indebted to Dr. Endre A. Balazs andDr. Charles L. Schepens for their guidance and continued support .

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Fessler JH (1960) A st ructural function of mucopolysaccharidesin connective tissue. Biochem J 76:124-132Foos RY, Wheeler NC (1982) Vitreoretinal junc ture : synchysissenilis and posterior vitreous detachment. Ophthalmology89:1502-1512Gelman RA, Blackwell J (1974) Inte ract ions between mucopolysac-charides and cationic polypeptides in aqueous solutions: hya-luron ic acid, heparit in sulphate and keratan sulphate. Biopoly-mers 13 : 139-156Hirokawa H, Takahashi M, Trempe CL (1985) Vitreous changesin peripheral uveitis. Arch Ophthalmol 103 : 1704-1707Jalkh A, Takabashi M, Topilow HW, Trempe CL, McMeel JW(1982) Prognostic value of vitreous findings in diabetic re tino-pathy. Arch Ophthalmol t00:432434Larsson L, Osterlin S (1985) Posterior vitreous detachment. A com-bined clinical and physiochemical study. Graefe 's Arch ClinExp Ophthalmol 233:92-95Ogston AG, Phelps CF (1961) The par tit ion of solutes betweenbuffer solutions contain ing hyaluronic acid. Bioehem J78 : 827-833O'Malley P (1976) The patte rn of vitreous syneresis - a study of800 autopsy eyes. In: Irvine AR, O'Malley C (eds) Advancesin vitreous surgery. Thomas, Springfield, pp 17-33Schepens CL (1983) Retinal detachment and allied diseases, vol 1.

Saunders, Philadelphia, pp 37-67Schepens CL, Avila MP, Jalkh AE, Trempe CL (1984) Role ofvitreous in cystoid macular edema. Surv Ophthalmol 28(suppl): 499-504Sebag J, Balazs EA (1984) Pathogenesis of cystoid macular edema:an anatomic considera tion of vitreoretinal adhesions. SurvOphthalmol 28 [Suppl] :493M98Sebag J, Balazs EA (1985) Human vitreous fibres and vitreoretinaldisease. Trans Ophthalmol Soc UK 104:123-128Sebag J, Balazs EA, Flood M T (1987) The fibrous structure ofhuman vitreous. Exp Eye Res (in press)Snowden JM (1982) The stabiliza tion of in vivo assembled collagenfibrils by proteoglycans/glycosaminoglycans. Biochim BiophysActa 706:153-157Snowden JM, Swann DA (1980) Vitreous structure. V. The mor-phology and thermal stability of vitreous collagen fibers andcomparison to the arti cular cartilage. Invest Ophthalmol VisSci 19:610- 618

Received September 12, 1986 / Accepted January 1, 1987