vitreoretinal reactions and persistent hyaloid vessels · anomaly (orts llorca and genis gilvez,...

Brit. J. Ophthal. (1976) 6o, 829

Vitreoretinal reactions and persistent hyaloid vessels

FRITZ H. STEFANI AND W. ANNA LASZCZYK*From the University Eye Hospital, Munich

In the large series of cases of pseudoglioma reportedby Howard and Ellsworth (I965) the conditions ofpersistent hyaloid vessels (PHV) or persistentprimary vitreous (PPV) often occurred as a singleanomaly, but only rarely as part of a syndrome-for example, Reese's dysplasia, Heine-Norrie'sdisease, incontinentia pigmenti Bloch-Sulzberger,Laurence-Moon-Bardet-Biedl's syndrome, chro-mosomal anomalies of group D.

Retinal changes may be combined with PHVand PPV-that is, with retinal folds (Mackensen,1953), falciform retinal detachment (v. Barsewisch,I968), areas of chorioretinal atrophy (Gloor, 1975),or atypical retinal detachment (Gloor and Haller,I968). Retinal dysplasia is a lesion more often foundin association with complex anomalies; Ricci (I969)used the term vitreoretinal dysplasia for such cases.

Vitreoretinal adhesions (Mann, 1935) have beenshown experimentally to occur as a developmentalanomaly (Orts Llorca and Genis Gilvez, I960).Tripathi and Ashton (197I) found that vaso-glialconnexions were normal in the adult rabbit. Vitreo-retinal strands in man are regarded as beingdegenerated vitreoretinal anastomoses of bloodvessels (Hagedoorn and Sieger, I956; Reese, I955;Wolter and Flaherty, I959; Spaulding and Nau-mann, I967; Giirtner, I964). These strands arealso seen in cases of non-oxygen induced retinitisproliferans in full-term infants (Stefani and Ehalt,I974). The observation that retinitis proliferansoccurs with other anomalies (Kriimmel and Rausch,1955; Benedikt and Ehalt, 1970; Addison, Font,and Manschot, 1972; Stefani and Ehalt, 1974;Best and Rentsch, 1974) is of importance regardingthe mechanism of lesions that histologically mimicretrolental fibroplasia but which occur in childrenwho have not received oxygen treatment, and ofpossible significance in understanding the mechan-ism that leads to fibroplasia.We have records of only eight cases of PPV,

relatively few compared with other hospitals(Manschot, i958; Font, Yanoff, and Zimmerman,i969; Jensen, I968), but these are sufficient to

Supported by a grant from the Alexander von Humboldt-Stiftung

Address for reprints: Dr F. Stefani, Augenklinik der UniversitltMunchen, 8 Munchen iS, Mathildenstrasse 8, W. Germany

advance some views of vitreoretinal reactionsinduced by persistent vascularized tissue within theeye; in cases which mimic retrolental fibroplasiathe blood vessel formation was of especial interest.

MaterialEach of the eight cases had been full-term and only oneinfant (Case 4) had received oxygen treatment becauseof cyanosis (Table I). The particulars of the clinical andmacroscopical findings are given in Table II. Case 4was clinically suggestive of I3-15 trisomy. The diagnosisof PPV was not made clinically.

HISTOLOGICAL FINDINGS (Table III)

Persistent primary vitreous (PPV)The appearance of PPV varied considerably from loosecellular forms similar to normal (embryonic) primaryvitreous (Cases i, 2, and 3) to firm fibrous or scarlikeforms (Cases 4, 5, 6, and 8). One (Case 7) showed afatty transformation and another (Case 4) containednests of chondroid tissue. The cellular form containedmainly two cell types, of fibroblastic and macrophagicvitreo-cystoid elements arranged in a netlike pattern.In a few sections in Case i, a large intracellular periodicacid-Schiff-positive globule resembling a corpus amy-laceum could be seen, but it was not possible to classifythe surrounding cell. This cellular form of PPV wasusually well vascularized while the fibrous form showedonly poor vascularization, as did the form showingfatty degeneration.

Persistent hyaloid vessels (PHV)Not all cases showed an obvious or patent persistenthyaloid artery (PHA) or vasa hyaloidea propria. Signs ofobliteration of the PHA (thickening of the tunica intimaand delamination of the internal elastic membrane withnarrowing of the lumen) were not seen. The hvaloidblood vessel system was particularly prominent in CasesI to 3. Patent anastomosing vitreoretinal blood vesselswere present in Cases I, 2, 4, and 8 (Fig. i). There weresome glial cells sheathing the preretinal portion of theblood vessel anastomoses and prominent vitreoretinalstrands were usually observed near by in these cases.These vitreoretinal strands consisted of a cellular (glial)portion on the retinal side which became fibrillarytowards the vitreous. In some there were signs oftraction along the strands with formation of retinal folds

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830 British Journal of Ophthalmology

Table I General clinical findings in eight casesCase Other clinical~~

Case Other clinical(no.) Sex Age 02 Other eye malformations

I Boy s month - Normal -

2 Girl 3 months - Normal -

4 months - Normal

I month + Cryptophthal- Cardioversion, hypoplasiamus of the lungs intestinal

abnormalities

5 Boy s3 years - Normal

6 Boy 6 months - Normal

7 Boy 4 years - Normal

8 Boy 5 years - Normal

Table II Clinical and macroscopical findings in

fings

almusCorneal cloudingCataractous lens

2 MicrophthalmusCataractous lens

3 Leucocoria

Macroscopical findings

Large globeIntracorneal filtering bleb (due to

partial absence of Descemet'smembrane)

Small cataractous lens withcalcification

PHV and PPVTunica vasculosa lentis

Small globeCataract, posterior lenticonusTotal retinal detachment

Total retinal detachmentIridocorneal adhesionsPre- and intraretinal haemorrhages

4 Suspected crypt- Cryptophthalmus, marked micr-ophthalmus or ophthalmusanophthalmus Sclerocornea

Obliterated anterior chamberSmall cataractous lens with

calcificationConnective tissue with chondroidal

deposits in front of the foldednasal retina

5 Cataractous lenssince birth

GlaucomaHyphaema

Cataractous, partly calcified lens,falciform retinal detachmentnasally with adhesion to the lens

6 Microphthalmus Small globeSclerocornea AphakiaLeucocoria Suspected ciliary and optic coloboma

Retinal detachment

7 HydrophthalmusLeucocoria

8 MicrophthalmusChoroidal colobomaCataract

Large globeFatty tissue in the posterior chamber

area (PPV?)

Small globeChoroidal colobomaCataractous lensPPVTotal retinal detachment

Other clinical findings Cause of enucleation

Hydrophthalmus

Grandmother 47 years old, myopic; Suspected retinoblastomamother 22 years old, myopicwith peripheral retinal degenera-tion, holes and marked pupillarymembrane; aunt 23 years old,myopic; uncle 14 years old, myopicwith peripheral retinal degenera-tion and retinal holes

Suspected retinoblastoma

Cyanosis, death due to pneumonia Necropsy

Secondary glaucoma

NMaternal bleeding at 4 to 6 months Suspected retinoblastoma

Hydrophthalmus

Suspected intraocular tumour

(Fig. 2). Sometimes there was a close spatial relationshipof PHV to the retina (Fig. 3) which was avascular inthese areas. In three (Cases 2, 3, and 8) there was newvessel formation on the surface of an avascular retinalarea (Fig. 4); there were no intraretinal glomeruloidendothelial proliferations suggestive of proliferation ofretinal vessels but there were connexions to the vasahyaloidea propria.

Retinal vascular changesThe avascular retinal areas were present mainly in thetemporal periphery (Cases I to 4, and 8), althoughthere was an avascular retinal area on the nasal side insome cases. In two cases, the vascular system washypoplastic-for example, smaller blood vessels withwide intercapillary spaces. In the case of falciform retinaldetachment there was a marked fibrosis of blood vesselsin the area of attachment. In only one case did theretinal vascular system appear normal. In three eyeswith peripheral temporal avascular retina, there werethe already described new vessel formations on theretinal surface of these areas.

Structural retinal changesChanges of the retinal structure were mainly due to lossor rarefaction of ganglion cells or microcystoid degenera-tion. Other changes present were various degrees ofgliosis, retinal dysplasia, or cystic retinoschisis. Retinalfold fornations by contracted vitreoretinal strands havealready been mentioned.

Associated ocular changesThere were other changes associated with these casesof PPV-for example, hypoplasia of the anterior seg-ment, cataracts and colobomata-but these are men-tioned here only for the sake of completing thehistological findings.

3 Boy4 Girl

enucleated eyes

Case(no.) Clinical find

I Hydrophtha



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Vitreoretinal reactions and persistent hyaloid vessels 831

Table III Histology of vitreoretinal changes in eight cases

PPV

+(Anterior and

posterior)

(Anterior andposterior)

Vitreoretinalanastomoses ofblood vessels

Proliferatingpreretinal blood Retinal vascular changesvessels

- Peripheral temporal retinawith avascular areas

+

(Anterior andposterior)

+

4 +(No obvious (With chondroidal

persistent changes)hyaloid artery)

5 +(Not patent) (Except for

adhesion of PHV

Peripheral nasal andtemporal retina withavascular areas

Peripheral nasal andtemporal retina withavascular areas

Peripheral temporal retinawith ava3cular area

Temporal retina: hypo-plastic vascularization

Nasal retina: fibrosis ofblood vessels

Changes in retinal structure

Rarefaction of ganglion cell layerMicrocystoid degeneration at

the posterior pole

Retinal foldsMicrocystoid degenerationGanglion cell layer rarefactionGliosis

Intraretinal haemorrhagesMicrocystoid degenerationLoss of ganglion cellsGliosis

Nasal retina: loss of the innerlayers, outer layers intact;dysplastic areas

Temporal retina: loss of ganglioncells, microcystoiddegeneration

Nasal retina: cysticretinoschisis

6 - +

7 Not obvious +(With fatty

degenerationVitreoretinal strands

Hypoplastic retinal blood Retinal foldsvessels Rarefaction of inner layers

- Loss of inner layersSome microcystoid degeneration

Peripheral temporal retina Loss of ganglion cellswith avascular area Marked gliosis

DiscussionDuring normal development, the hyaloid vascularsystem precedes retinal vascularization and under-goes involution at the seventh month. A persistentvascular system with surrounding connective tissuein the vitreous cavity is likely to be a potentialfactor in the induction of reactive developmentalchanges in other intraocular structures.

Vascular vitreoretinal anastomoses and vitreo-retinal strands (Reese and Straatsma, I958; Mans-chot, 1958; Wolter and Flaherty, 1959; Giirtner,I964; Spaulding and Naumann, I967) may beregarded as reactive tissue changes caused bydisturbed involution of the primary hyaloid system.

Avascular retinal areas have previously beenobserved in incontinentia pigmenti or the Bloch-Sulzberger syndrome (Best and Rentsch, I974).Our observation of peripheral avascular retinal areas

in eyes of infants between the ages of one month-and four years born at full-term is in contrast withthat of Reese and Blodi (i949) and Reese (I955)who described a fully developed retina in PPV. Thepersistence of an avascular retina shows there is noneed for retinal vascularization and suggests there s

an adequate oxygen supply to this area of retinafrom the choroidal or vitreous aspects; in our cases

this may be due to an increased oxygen level on thevitreous side with its abnormal vascular system(although there is also the possibility of earlydegenerative retinal changes and a consequentdecreased oxygen demand). The same applies to a

hypoplastic vascular system. The degree andmorphological expression of the various factorsinvolved (Table IV) in the abnormally developingeye may vary widely, and the lack of knowledge ofthe early stages of PPV would make further state-ments purely speculative. But with regard tovascularization of the developing intraocular tissues,especially in malformed eyes, we would expectreactions as long as involution, degeneration, andtissue growth have not reached a final stage in whichthe blood vessel system covers the oxygen need ofthe tissues sufficiently. Massive new vessel forma-tion is a response to hypoxia which is not necessarilypermanent.

According to Foos and Kopelew (O973) the retinalvascular system is complete in only Io per cent offull-term infants. We still see oxygen-inducedretrolental fibroplasia although mainly in pre-

maturity and rarely is there an equivalent in full-term infants; thus an incomplete retinal vasculariza-tion at birth does not necessarily imply retinal

Case PHV(no.)

I +

2 +

3 +

8 + + + +



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832 British J7ournal of Ophthalmiiology

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Table IV Possible factors inducing developmentalor reactive vitreoretinal changes

Persistent primary vitreozcs (PPV) tissuesInvolutionHaemodynamicsHypoxiaDegenerationReactive growth

Retinal tissues

FIG. I Case i. Nasal retina showing vitreoretinalanastomrsis of blood vessels (arrow) and vitreoretinalstrands. Haematoxylin and eosin. x I40

ischaemia and with it the risk of retrolental fibro-plasia. The persistence of intravitreal blood vessels,however, raises the question whether these vesselsmay proliferate under certain conditions and thusmimic the proliferative phase of retrolental fibro-plasia. Indeed, Gyllensten and Hellstr6m (I1954,I955), Patz (I965), and Ashton (I968) showed inanimal experiments that oxygen could induce aproliferation of persistent hyaloid vessels. Wenoticed formations of new vessels on the surface ofperipheral avascular retinal areas that had conne-xions with the hyaloid system and the absence ofintraretinal endothelial proliferation indicates ahyaloid origin. Krdmmel and Rausch (I955) andBenedikt and Ehalt (I970) have suggested that theformations of new vessels in incontinentia pigmentiare supplied from the hyaloid artery, while Best andRentsch (I974) in their case suggested that theywere supplied by the retina. So it appears possiblethat both vascular systems may play a role in theformation of new vessels and ischaemic retinalareas may play a pathogenetic role. This seems ofimportance in some hitherto unexplained cases of

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FIG. 2 Case i.Temporal retinawith a vitreoretinalstrand andfornmatiotrof a retinal fold inthe area of traction.Note also theischaemic changes iusthe inner retina.Haematoxylin andeosin. X140

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Vitreoretinal reactions and persistent hyaloid vessels 833

cluding vitreoretinal anastomoses of blood vessels,vitreoretinal strands, traction folds of the retina,avascular retinal areas, hypoplasia of retinal bloodvessels, rarefaction of retinal ganglion cells, andischaemic structural changes of the retina. Newvessel formation on the surface of avascular retinalareas was supplied from persistent hyaloid bloodvessels. This finding may be of some importancein explaining those cases histologically resemblingclassical retrolental fibroplasia with no history of

0. prematurity or oxygen treatment.

A-i

WX'S.41u#O4AV,A5,14s.ws s~~~~~~~~0 tR aw ....... \ ....si .

;."...'.FIG. 3 Case 2. Close spatial relationship of persistenthyaloid blood vessels to the avascular retina. Haematoxylinand eosin. x I40

non-oxygen induced retinitis proliferans in full-term infants.That ischaemic changes take place is further

shown by the finding of microcystic retinal degener-ations and the loss of ganglion cells, althoughchanges of intraocular pressure must also be takeninto account.

SummaryIn cases with persistent primary vitreous in full-term infants there were vitreoretinal reactions in-

FIG. 4 Case 2. Neovascularization on the avascularretinal surface. Retina shows marked ischaemic changes.Haematoxylin and eosin. x I40

References

ADDISON, D. J., FONT, R. L., and MANSCHOT, W. A. (1972) Amer. Y. Ophthal., 74, 697ASHTON, N. (1968) Brit. 3t. Ophthal., 52, 505BARSEWISCH, VON B. (I968) Ber. dtsch. ophthal. Ges., 68, 48IBENEDIKT, O., and EHALT, H. (I970) Klin. Mbl. Augenheilk., 157, 652BEST, w., and RENTSCH, F. (1974) Ibid., 164, 19



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834 British Journal of Ophthalmology

FONT, R. L., YANOFF, M., and ZIMMERMAN, L. E. (I969) Arch. Ophthal., 82, 43FOOS, R. Y., and KOPELEW, S. M. (1973) Surv. Ophthal., I8, 117GARTNER, J. (I964) V. Graefes Arch. Ophthal., I67, 103GLOOR, B. P. (I975) Klin. Mbl. Augenheilk., I66, 293

, and HALLER, R. (I968) V. Graefes Arch. Ophthal., 175, 193GYLLENSTEN, L. J., and HELLSTROM, B. E. (1954) Acta paediat. (Uppsala), 43 (suppI. I00), 131

, and (I955) Amer. J. Ophthal., 39, 475IHAGEDOORN, A., and SIEGER, D. H. (1956) Ibid., 49, 66oHOWARD, G. H., and ELLSWORTH, R. M. (I965) Ibid., 6o, 6ioJENSEN, 0. A. (I968) Acta ophthal. (Kbh), 46, 418KRUMMEL, H., and RAUSCH, L. (1955) Ophthalmologica (Basel), 130, 31MACKENSEN, G. (I953) Klin. Mbl. Augenheilk., 123, 41MANN, I. (I935) Brit. J. Ophthal., 39, 641MANSCHOT, W. A. (1958) Arch. Ophthal., 59, i88ORTS LLORCA, F., and GENIS GALVEZ, J. M. (I960) Arch. Soc. oftal hisp.-amer., 20, 91PATZ, A. (I965) Invest. Ophthal., 4, 988REESE, A. B. (I955) Amer. J. Ophthal., 40, 3I7

and BLODI, F. C. (I949) Ibid., 33, 23, and STRAATSMA, B. R. (1958) Ibid., 45, I99

RICCI, A. (I969) J. Gindt. hum., 17, suppi. ISPAULDING, A. G., and NAUMANN, G. (I967) Arch. Ophthal., 77, 666STEFANI, F. H., and EHALT, H. (I974) Brit. J. Ophthal., 58, 490TRIPATHI, B., and ASHTON, N. (1971) Ibid., 55, IWOLTER, J. R., and FLAHERTY, N. (1959) Amer. J. Ophthal., 47, 491



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