Ultrastructural Studies of Vitreomacular Traction

Syndrome

William E. Smiddy, M.D., W. Richard Green, M.D., Ronald G. Michels, M.D.,and Zenaida de la Cruz, B.S.

We performed electron microscopic studi~son seven specimens removed from the postert­or retina at the time of vitrectomy for vitreo­macular traction syndrome. Fibrous astrocyteswere the predominant cell type in all cases.Fibrocytes were present in two cases andmyofibrocytes were seen in three cases. Addi­tional cellular and extracellular features in­cluded fragments of internal limiting mem­brane in six cases, old collagen in all cases,new collagen in one case, occasional macro­phages in four cases, and fibrous astrocyteswith myofibroblastic differentiation in onecase.

THE VITREOMACULAR TRACTION syndrome iscaused by vitreous traction on the macula,usually because of an incomplete posterior vit­reous detachment. The most common morpho­logic configuration is a vitreous .deta~hmentperipheral to a zone where th~ cortical vltreo~sremains attached to the retina at the opticnerve head and the macula. Traction on themacula causes decreased vision, metamor­phopsia, photopsia, and micropsia."! Clinicaland operative evaluation has disclosed a visibleepiretinal membrane, a layer of cortical vitre­ous, or both over the posterior pole.

Traction on the retina can be effectively elimi­nated by removal of the epiretinal membraneand condensed vitreous over the posteriorpole." We studied the electron microscopic fea­tures of epiretinal tissue removed from theposterior pole in seven cases of vitreomaculartraction syndrome.

Accepted for publication Nov. 3, 1988.From the Vitreoretinal Surgery Service and the Eye

Pathology Laboratory, Wilmer Ophthalmologic Insti­tute, Johns Hopkins University, Baltimore, Maryland.Dr. Smiddy is a 1987-1988 Heed Ophthalmic Foundationfellow.

Reprint requests to W. Richard Green, M.D., EyePathology Laboratory, The Johns Hopkins Hospital, 600Wolfe St., Baltimore, MD 21205.

Material and Methods

The excised specimens were placed in buf­fered solution containing 4% formaldehydeand 2.5% glutaraldehyde and postfixed with2% phosphate-buffered osmium tetroxide.After dehydration, the tissue was embedded inepoxy resin. Semithin sections were stainedwith paraphenylenediamine for phase-contrastmicroscopy. Ultrathin sections were doublystained with uranyl acetate and lead citrate andexamined in a transmission electron micro­scope.

Results

Clinical findings-The clinical features of ourseven patients with vitreomacular traction syn­drome (Table 1) were similar to those report­ed previously in a larger clinical series." Theaverage age was 61 years and there were fivewomen and two men. Preoperative visual acu­ity ranged from 20/60 to 11200, and averaged20/200. Cystic changes in the macula were pres­ent in six cases (Fig. 1).

The vitreoretinal anatomy, observed duringsurgery, was of two basic patterns. In fivecases, the cortical vitreous was detached in allfour quadrants peripheral to the macula andoptic nerve head. In two cases there was vitre­ous detachment in two to three quadrants withresidual attachment to the macular area. Theposterior vitreous surface was usually visiblepreoperatively where it was separated from theretina, but it was nearly transparent and couldnot be photographed. Postoperative visual acu­ity improved in five cases and was unchangedin two during a follow-up interval ranging fromsix to 21 months (mean, 7.7 months).

Pathologicfindings-Transmission electron mi­croscopy disclosed four morphologically dis­tinguishable cell types as determined by previ-

©AMERICAN JOURNAL OF OPHTHALMOLOGY 107:177-185, FEBRUARY, 1989 177

178 AMERICAN JOURNAL OF OPlITHALMOLOGY

TABLE 1

CLINICAL FEATURES OF PATIENTS WITH VITREOMACULAR TRACTION SYNDROME

February, 1989

DURATION PREOPERATIVE POSTOPERATIVEPATIENT NO., OF VISUAL VITREORETINAL VISUAL FOLLOW·UP

AGE (YRS), SEX SYMPTOMS (MOS) ACUITY ANATOMY' ACUITY (MOS)

1,82, M 12 20/200 A 20/100 1 13

2,58, F 12 20/300 A 20/100 1 10

3,63, M 11 20/60 B 20/20 21

4,69, F 3 20/80 A 20170 6

5, 75, F 10 20/200 A 20/200 6

6,47, F 1 1/200 A 20/400 9

7,57, F 5 20/200 B 20/200 6

•A, peripheral posterior vitreous detachment in all four quadrants; B, detachment in two or three quadrants, but with zoneof persistentattachment over the maculaand optic nerve head.

'Postoperative visualacuity was limitedby progressive nuclearsclerosis of the crystalline lens.

ously reported criteria (Table 2).8-16 Fibrousastrocytes were the predominant cell type in allcases (Figs. 2 through 6) and were character­ized by masses of intracytoplasmicintermediate-type lO-nm filaments, junctionalcomplexes of the adherence type, and large,fusiform cells in groups or a monolayer show­ing polarization with basement membrane pro­duction. The fibrous astrocytes in one casecontained aggregates of 5- to 7-nm intracyto­plasmic filaments with fusiform densities(Fig. 5).

Other cell types were less frequent. Fibro­cytes were identified in two cases and werecharacterized by abundant rough endoplasmicreticulum and a prominent Golgi complex, fusi­form shape of the nucleus and cell body, andabsence of intracytoplasmic filaments or base­ment membrane. Myofibrocytes were presentin three cases and displayed features of fibro­cytes but with aggregates of 5- to 7-nmsubplasmalemmal cytoplasmic filaments withfusiform densities. Macrophages were presentin four cases, identified by the presence of

Fig. 1 (Smiddy and associates). Fluorescein angiographic appearance of Case 3. Early (left) and late (right)frames showing mild cystoid macular edema.

Vol. 107, No.2 Vitreomacular Traction Syndrome

TABLE 2ULTRASTRUCTURAL FEATURES OF VITREOMACULAR TRACTION SYNDROME

179

FIBROUS ASTROCYTESINTERNAL WITH

PATIENT CELL TYPES' LIMITING MYOFIBROBLASTICNO. PREDOMINANT OTHER MEMBRANE COLLAGEN! DIFFERENTIATION

1 FA FC,MFB,M Yes New and old No2 FA Yes Old No3 FA M Yes Old Yes4 FA Yes Old No5 FA FC,MFB,M Yes Old No6 FA MFB Yes Old No7 FA M No Old No

'FA, fibrous astrocytes; FC, fibrocytes; MFB, myofibroblasts; M, macrophages.

!Collagen was judged to be new if it measured greaterthan 16 nm in diameterand old if it measured lessthan 16 nm.

pleomorphic intracytoplasmic contents, irregu­larly shaped cell body and nucleus, andmembrane-bound groups of granules of vary­ing electron density.

Internal limiting membrane was present insix cases and had a smooth inner surface and anirregular outer surface. The smooth internalsurface served as a substrate for the cellulargrowth in five of the seven membranes. In twocases (Cases 1 and 2), a thin layer of corticalvitreous with 15-nm diameter collagen waspresent between the internal limiting mem­brane and the cell layer.

Extracellular collagen was frequently associ­ated with the cells and usually measured lessthan 15 nm in diameter, indicating that it wasprobably native collagen of the cortical vitre­OUS. 17

Discussion

The ultrastructural features of epiretinalmembranes in this series of cases of the vitreo­macular traction syndrome are similar to thosein some cases of idiopathic epiretinal mem­branes. However, the clinical features of thevitreomacular traction syndrome are distinctlydifferent from those of idiopathic epiretinalmembranes. The vitreomacular traction syn­drome is characterized by an incomplete pos­terior vitreous detachment."? whereas eyeswith idiopathic epiretinal membranes involv­ing the macula have a high rate of complete

posterior vitreous detachment as shown clini­cally16,18,19 and histopathologically. 8,10,20 Idio-pathic epiretinal membranes have been notedto occur up to three years after the posteriorvitreous detachment."

One case of the vitreomacular traction syn­drome has previously been studied histopatho­logically by light microscopy," but in this caseonly a strand of vitreous was attached to themacula. There was no epiretinal membrane andthere was considerable postmortem autolysis.This configuration of vitreomacular tractionwas found in only two of 16 eyes in a series ofsurgical cases reported previously,7and it wasnot present in the current series.

The electron microscopic features of the spec­imens in the current series included all celltypes previously observed in epiretinal mem­branes except retinal pigment epithelium cells.The most striking finding was the predomi­nance of fibrous astrocytes. Each major celltype may have particular roles or associationsin various vitreoretinal disorders, but thereprobably is considerable overlap.

Retinal pigment epithelium cells predomi­nate in cases of proliferative vitreoretinopathy"and cases of macular pucker after retinal de­tachment. 13,15,16,24 Although many of these epi­retinal membranes also contain fibrousastrocytes,9,12,25,26 no definite retinal pigment ep­ithelium cells were identified in this series.Some studies suggest that fibrocytes andmyofibrocytes are derived from retinal pigmentepithelium cells,23,27,28 and the contractile prop­erty of myofibrocytes is thought to account for

180 AMERICAN JOURNAL OF OPHTHALMOLOGY February, 1989

Fig. 2 (Smiddy and associates). Case 6. Membrane is composed of fibrous astrocytes that have a multilayeredgrowth pattern with basement membrane (arrowheads) and characteristic lO-nm diameter intracytoplasmicfilaments (inset) (x 14,000; inset, x 56,000).

clinical features of tractionon the retina. In thisseries, myofibrocytes were identified in twocases with especially severe clinical features oftraction, but there was no evidence that they

were derived from retinal pigment epitheliumcells.

The predominance of fibrous astrocytes inthe current series suggests that migration and

Vol. 107, No.2 Vitreomacular TractionSyndrome 181

.Fig. 3 (Smiddy and associates). Case 3. The epiretinal membrane is composed of a monolayer of fibrousastrocytes with basement membrane formation (arrowheads) on a collagen base. Marginal aggregates of 5- to7-nm microfilaments (arrows) indicate myofibroblastic differentiation. A macrophage is also present (lower left)(x 5,400).

proliferation of these cells may be a secondaryresponse to vitreoretinal traction. In the ab­sence of retinal breaks, fibrous astrocytes fromthe retina would have ready access to the inner

retinal surface since the internal limiting mem­brane is discontinuous over the optic nervehead in normal eyes," and small breaks in theinternal limiting membrane may occur in other

182 AMERICAN JOURNAL OF OPHTHALMOLOGY February, 1989

locations due to vitreous traction." Focalepipapillary plaques of proliferating glial cellshave been identified in 27% of eyes at autopsy"and in 46% of eyes with a posterior vitreousdetachment." Defects in the internal limitingmembrane in the fovea, over retinal vessels, orelsewhere are clinically undetectable and theymay be self-sealing so they would be undetect­able by histopathologic study." Traction by apartial posterior vitreous detachment servingas a stimulus for cell migration and prolifera­tion has been hypothesized in othercases lO,20,29,31 The cases in the present series hadchronic traction involving the macula and opticnerve head. The stimulus of vitreoretinal trac­tion combined with the framework of the adja­cent cortical vitreous may account for the mi­gration and proliferation of glial tissue.

Another possible explanation for the cellular

Fig. 4 (Smiddy and associates). Case 3. High­er power view of a fibrous astrocyte showsbasement membrane (top, arrow) and lO-nmcytoplasmic filaments (between arrowheadsand bottom) (top, x 10,000; bottom, x 44,000).

features in the tissue examined in this series isthat epiretinal membranes may have formedbefore the posterior vitreous detachment oc­curred and caused a firm attachment betweenthe cortical vitreous and the retina, therebypreventing separation in that region. However,the configuration of the zone of vitreoretinaltraction in these cases is consistent? and unlikethat encountered in other cases of epiretinalmembranes. Posterior vitreous detachment isconsidered to predate the formation of idio­pathic epiretinal membranes."

In the current series, portions of internallimiting membrane were present in six of sevensamples. Fragments of internal limiting mem­brane are also common in specimens of epireti­nal membranes removed by vitreous surgery,but this is generally not associated with recur­rent membrane proliferation.":" This suggests

Vol. 107, No.2 Vitreomacular Traction Syndrome 183

Fig. 5 (Smiddy and associates). Case 3. Top, Monolayer of fibrous astrocytes with basement membrane(arrowhead), aggregates of 5- to 7-nm microfilaments (arrow), and large bundles of lO-nm filaments (bracket andinset). Apparent contraction of cellular layer had a gathering effect on the collagen base (x 10,000; inset,x 54,000). Bottom, Another fibrous astrocyte showing basement membrane (arrowhead) and an apparenttension line of marginal aggregates of 5- to 7-nm microfilaments with fusiform densities (arrows) (x 12,000).

that breaks in the internal limiting membranemay not be the primary stimulus to outgrowthof glial tissue from the retina, and that structur­al factors such as vitreoretinal traction or bio-

chemical stimuli may modulate the process ofcell migration and proliferation.

The vitreomacular traction syndrome is adistinct clinical condition characterized by trac-

184 AMERICAN JOURNAL OF OPHTHALMOLOGY February, 1989

Fig. 6 (Smiddy and associates). Case 7. Top, Monolayer of fibrous astrocytes with basement membrane(arrows) and aggregates of 10-nm filaments (asterisk). A cell process of a fibrous astrocyte is lined by basementmembrane (arrowheads) (x 16,000). Bottom, Higher power view of fibrous astrocyte with basement membrane(arrow) and intermediate filaments (asterisk) (x 40,000).

tion on the posterior retina resulting from anincomplete posterior vitreous detachment. Assuch, the clinical pathoanatomy is differentfrom most cases of idiopathic epiretinal mern-

branes and from eyes with an impending macu­lar hole. 31 However, the ultrastructural featuresof epiretinal tissue from eyes with the vitreo­macular traction syndrome are similar to those

Vol. 107, No.2 Vitreomacular Traction Syndrome 185

from eyes with idiopathic epiretinal mem­branes, suggesting common features in patho­genesis.

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