dystrophy: valueof specular microscopy · Laganowski,Sherrard,Muir,Buckley Figure2 SpecularphotomicrographofsubtotalICEplusshowingICEissue(right-handside)clearlydemarcatedfrom...

BritishlournalofOphthalmology, 1991,75,212-216

Distinguishing features of the iridocornealendothelial syndrome and posterior polymorphousdystrophy: value of endothelial specular microscopy

Hania C Laganowski, Emil S Sherrard, Malcolm G Kerr Muir, Roger J Buckley

AbstractThe literature suggests that posteriorpolymorphous dystrophy (PPD) may showfeatures such as iridocorneal adhesions, glassymembranes, and pupillary ectropion which are

typically ascribed to the iridocorneal endo-thelial (ICE) syndrome. This complicatesdiagnosis. PPD, unlike ICE, is familial, andICE, unlike PPD, is usually progressive andfrequently complicated by glaucoma: thus it is

important to distinguish between them. Todetermine whether this could be achieved byspecular microscopy, since the posteriorcorneal surface is abnormal in both conditions,57 cases ofICE and 44 ofPPD were repeatedlyexamined and photographed with the specularmicroscope. Progressive and/or staticmorphological features of the corneal endo-thelium and Descemet's membrane were

found that were specific for each condition.Specular microscopy can thus provide a

definitive diagnosis of ICE or PPD even inuncertain cases.

Moorfields Eye Hospitaland Institute ofOphthalmology, LondonH C LaganowskiE S SherrardMG K MuirR J BuckleyCorrespondence to:H C Laganowski, MoorfieldsEye Hospital, City Road,London ECIV 2PD.Accepted for publication21 September 1990

The iridocorneal endothelial or ICE syndrome,which comprises Chandler's syndrome (CHS),progressive iris atrophy (PIA), and the irisnaevus (Cogan-Reese) (INS) syndrome, is a non-familial, usually unilateral anomaly of theposterior cornea and iris, the aetiology of whichis unknown.'

Posterior polymorphous dystrophy, or PPD,is generally regarded as an inherited, frequentlybilateral abnormality of the posterior, non-banded layer of Descemet's membrane, whichimplies that it is congenital and the result of ananomaly of the corneal endothelium at about thetime of birth.2The ICE syndrome is typically symptomatic

and is most commonly diagnosed in middle age.It is progressive and is frequently complicated byglaucoma and/or corneal decompensation.

Posterior polymorphous dystrophy has beendiagnosed in all age groups, usually as an

incidental finding, since it is typically asympto-matic. It is commonly non-progressive; onlyoccasionally is it associated with cornealdecompensation or glaucoma.2The universal clinical sign ofthe ICE syndrome

is a finely hammered silver appearance3'4 of all orpart ofthe posterior corneal surface when viewedin specularly reflected light with the slit-lamp.When only part of the posterior corneal surfaceappears as hammered silver, the remaining areasof endothelium are composed of either enlargedor exceptionally small cells.5 7 Dystrophic irischanges are almost always present. These range

from subtle stromal melting (as in CHS) to fullthickness iris 'melt' and/or 'stretch' holes (as inPIA) and the formation ofconstricted nodules onthe anterior iris surface (as in INS). Peripheralanterior synechiae commonly occur and are oftenaccompanied by corectopia and ectropion uveae.A glassy membrane may be visible bridging partofthe anterior chamber angle and adhering to theanterior surface of the iris.

Classically the diagnosis of PPD requires thepresence of small, round, discrete, transparent,vesicular lesions, surrounded by a ring ofopacity,at the level of Descemet's membrane.8 Otherfeatures in addition to vesicles are present inmany corneas, and this has led to subdivision ofPPD into descriptive categories.2 Vesicular PPDimplies the presence of vesicles alone; these maybe single, scattered, or grouped. A variant inwhich large and numerous patches of confluentvesicles occur is termed geographic PPD bysome authors.29 Band PPD is characterised byelongated, broad, band(s) of roughenedDescemet's membrane delineated by narrow,opaque, irregular ridges. Diffuse PPD involvesall or a large part of the posterior corneal surfaceand appears as swirled patterns of irregularthickening and opacification of Descemet'smembrane; it is often accompanied by full-thickness corneal oedema. Apart from a state-ment by Waring et al'I that the endothelium overthe PPD lesions is altered and an inference that itis normal elsewhere, there appears to be nopublished description of the endothelium inPPD as seen with the slit-lamp.Manyofthe clinical featureswhich are typically

ascribed to the ICE syndrome, such as broadperipheral iridocorneal adhesions, a glassy mem-brane on the iris surface, pupillary ectropion andraised intraocular pressure, have been reportedin cases of PPD.2891 1-1 Indeed Cibis et all3 statethat some patients withPPD 'meet the diagnosticcriteria of Chandler's syndrome'.

Ifthere is an overlap ofthe clinical signs ofICEand PPD it raises the possibility that the twoconditions are related. If this were so, then PPDshould be regarded as potential ICE, which isassociated with a higher incidence of compli-cations, most significantly glaucoma, and ICEshould be sought in the families of patients withPPD with a view to instituting early treatment.The possible occurrence of ICE-like features

in PPD may make its 'clinical differentiationfrom ICE difficult'.'4 The iridocorneal endo-thelial syndrome, which is non-familial, ingeneral has a poorer outlook for the affectedindividual than does PPD, which, beinginherited, has implications for the family. There-fore it is important to distinguish between ICE

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Distinguishingfeatures ofthe iridocorneal endothelial syndrome and posteriorpolymorphous dystrophy: value ofendothelial specular microscopy

and PPD at the clinical level to establish thecorrect prognosis and overall management(treatment, follow-up, screening) for the patientand his or her relatives. As a means to this end ithas been suggested that the corneal signs ofPPDare sought in the families of patients in whom adiagnosis ofCHS is being considered. 13 However,while inherited traits are significant, theirdisclosure is time consuming and expensive.Moreover, the finding of PPD vesicles in familymembers of patients with classic signs of ICEdoes not necessarily constitute a diagnosis ofPPD in those patients, as suggested by someauthors.8 It would be preferable and moreprecise if the distinction between ICE and PPDcould be based only on the clinical signs of thepatients. Since an anomaly of the corneal endo-thelium probably underlies both disorders andmany of the corneas affected by either remainclear for many years, if not indefinitely, endo-thelial specular photomicroscopy (ESP) has thepotential to reveal features at the cellular levelwhich may distinguish between ICE and PPD.

This communication compares and contraststhe ESP findings in 57 cases ofthe ICE syndromewith those in 44 cases ofPPD.

Material and methodsAll the patients in this series were selected fromthose referred with a probable clinical diagnosisofICE orPPD to a special study group. Selectionwas based on the slit-lamp appearance of eachcase. To be included in the series as ICEdepended on the presence of a hammered silverappearance of the posterior corneal surface andthe absence of vesicles and, as PPD, on thepresence of classic vesicles in one or both eyeswith or without other features ofPPD.The 57 cases of ICE comprised 37 with

progressive iris atrophy, 18 with Chandler'ssyndrome, and two with iris naevus syndrome.All were unilateral.

In accordance with the subdivision outlinedby Waring et all 19 of the 44 cases of PPD wereclassified as vesicular PPD. Of these, 15 werebilateral, one was unilateral, and three weremonocular, to give a total of 34 affected eyes.Twenty-three cases were classed as band PPD.Posterior polymorphous dystrophy bands (inaddition to vesicles) were present in both eyes infour and in one eye in 19 cases. Of the latter theother eye showed vesicles alone in five cases andwas normal in the remaining 14. Of the 27 eyeswith PPD bands 23 had a single band and fourhad two. Two cases, both bilateral, were classedas diffuse PPD.None of the eyes with PPD showed the iris or

anterior chamber angle changes typicallyassociated with ICE, or any other ocularabnormality.The Pocklington, Keeler/Konan large field

specular microscope was used throughout thestudy. At least 15 specular photomicrographswere taken of the posterior corneal surface ofeach affected eye, and a representative sample ofpictures was taken of the contralateral normaleye in unilateral cases. Many of the cases weresimilarly examined on multiple occasions at six-monthly intervals over several years.

ResultsThe ESP appearances are here summarised; theyhave been described in detail elsewhere.7 15

IRIDOCORNEAL ENDOTHELIAL SYNDROMEIn all cases of the ICE syndrome specularmicroscopy revealed the presence of abnormalcells (Fig 1), characterised by a dark area with alight central spot and often a light peripheralzone. Sometimes dark cell margins were visible.The cells varied in size but typically were largerthan normal endothelial cells. They occurred inthe areas that appeared as hammered silver with

Figure 1 Specular photomicrograph oftypical ICE cells, which appear as a negative ofnormal endothelium, from a case oftotal ICE. (Bar=O 1 mm.)

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Laganowski, Sherrard, Muir, Buckley

Figure 2 Specular photomicrograph ofsubtotalICE plus showingICE issue (right-hand side) clearly demarcatedfromendothelium composed ofvery small, distinct cells. An isolated patch ofICE tissue (an ICE-berg) lies within the endotheliumdistorting adjacent cells. (Bar=0 1 mm.)

the slit-lamp. These cells are regarded aspathognomonic ofthe ICE syndrome and so havebeen termed ICE cells and the tissue they formICE tissue.7The ICE cells or tissue and the remaining

endothelial cells formed four basic patterns:7(1) Disseminated ICE occurred in seven cases.

It showed ICE cells scattered throughout avaguely defined endothelial mosaic which wasmade up of larger than average cells.

(2) Total ICE (Fig 1) was found in 17 cases.Here the entire posterior corneal surface wascovered by ICE tissue and no normal endo-thelium was apparent.

(3) Subtotal ICE plus (Fig 2) occurred in 23cases. It was characterised by an area of clearlydefined ICE tissue which covered from one to

three-quarters of the posterior corneal surfaceand tended to extend to, or arise from, beyondthe limbus. The inner edge of the ICE tissue wasfrequently sinuous and formed an abruptjunction with the remaining endothelium.Occasionally a small patch of ICE tissue wasisolated in the endothelium forming what hasbeen termed an ICE-berg7 (Fig 2). Endothelialcells were distinct and very small with a signifi-cantly greater cell population density than in agematched normal eyes. The cells adjacent to theICE tissue were often elongated parallel to itsedge (Fig 2).

(4) Subtotal ICE minus was found in 10 cases.Here a mass of ICE tissue merged often imper-ceptibly with the remaining endothelium, whichwas composed of greatly enlarged cells.

Figure 3 Specular photomicrograph ofclassic PPD vessicles appearing as clearly defined, dark rings. Endothelial cells'within' and 'without' the rings are parfocal and enlarged and undistorted. (Bar=0 1 mm.)

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Distinguishingfeatures ofthe iridocorneal endothelial syndrome and posterior polymorphous dystrophy: value ofendothelial specular microscopy

Figure 4 Specular photomicrograph ofPPD band showing endothelium on a strip of roughened Descemers membranedelineated by dark borders. Endothelial cells 'within' and 'without' the band are parfocal and greatly enlarged; many 'within'and on the borders are masked. (Bar=O I mm.)

Follow-up examination over several yearsrevealed that all cases originally classed asdisseminated ICE progressed to total ICE withan associated accelerated loss of cells. No signifi-cant changes occurred in total ICE. In thesubtotal variants there were changes in contourof the ICE tissue, but the population density ofICE cells remained relatively constant, while incases of subtotal ICE plus there was a significantincrease in the CPD of the endothelium.

POSTERIOR POLYMORPHOUS DYSTROPHYWith the specular microscope classic PPDvesicles appeared as dark rings with distinct,often scalloped edges surrounding a lighter,mottled centre (Fig 3). The relief image617 ofvesicles indicated that they were shallow, steepsided pits in the posterior aspect of Descemet'smembrane. A variable number of small blackspots often studded the endothelium and wereinterpreted as representing miniature vesicles.

In the specular, and relief mode, a PPD bandappeared as a strip of roughened Descemet'smembrane delineated by dark, frequentlyscalloped, approximately parallel borders (Fig4). In many examples these were apparentlycomposed of coalesced black discs (giving asimilar appearance to the black rings of vesicles)(Fig 4) and sometimes of confluent, small,complete vesicles. In others the appearance ofthe overall band was of a row of coalesced, largevesicles. A band usually terminated in separateor clusters of vesicles.

In the cases of diffuse PPD the entire posteriorcorneal surface was affected by swirled patternsof irregular features that were suggestive ofdistorted, incomplete, confluent vesicles.

In all cases of vesicular and band PPDrecognisable endothelial cells were visible overthe entire posterior corneal surface, includingthe vesicles and bands. Over the lesions, how-

ever, particularly on their dark, delineatingborders, the image of the cells was oftendiminished, indistinct, or partly masked becauseof optical effects of the lesions, but the cells werenot physically distorted (Figs 3, 4).The endothelium 'within' and 'without'

vesicles and bands was parfocal (Figs 3, 4). Thisindicates that it bridges rather than lines them.This in turn suggests that vesicles and bands arefilled.The endothelial cell population density was

reduced in all but three of the cases of vesicularPPD and was even lower in all cases ofband PPDcompared with age matched normal subjects. Inthe cases of diffuse PPD visible endothelial cellswere slightly larger than normal in one and wereofnormal size in the other.

Follow-up examination over several yearsrevealed no changes in the situation or con-figuration of PPD vesicles or bands. There wasno evidence of an accelerated rate of loss ofendothelial cells.

DiscussionRecent reports28 9 11-13 of the macroscopic featuresofthe ICE syndrome andPPD occurring togetherin an individual or separately in different mem-bers of a family have raised the possibility of alink between the two conditions. They have alsoled to confusion and disagreement about thediagnostic criteria.

Prior to these reports ICE and PPD have beenregarded as separate dystrophies because ofvarious differences between their modes ofpresentation, propensity for progression, finaloutcome, and, classically, their distinctive slit-lamp appearances. Moreover, histopathologicalstudies, though based only on decompensatedcorneas from each condition, reveal differencesin Descemet's membrane which make a relation-ship between ICE and PPD highly unlikely. 18

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Laganowski, Sherrard, Muir, Buckley216

A comparison of the specular microscopicalfindings of the posterior corneal surface in thisseries of cases of ICE and PPD appears todistinguish between the two conditions at theclinical level. No case ofPPD showed ICE cells.Although ICE-bergs and PPD vesicles may

appear to be analogous, an ICE-berg consists of anest of ICE cells, surrounded by a thin darkedge, lyingwithin the endotheliumand distortingthose cells adjacent to it (Fig 2), while a PPDvesicle is a pit delineated by a thick, dark borderand lying anterior to recognisable endothelialcells without distorting them (Fig 3). PPDvesicles and bands were shown to be fixedfeatures of the posterior cornea. ICE cells andtissue, including ICE-bergs, however, were notstable, particularly in the disseminated variant.Endothelial cells were recognisable as such inboth conditions, but in ICE they were mostcommonly much smaller (Fig 2), while in PPDthey were almost always much larger than normal(Figs 3, 4).The ESP findings in classic cases of ICE and

PPD were specific for each condition. On thebasis of this study, therefore, it is suggested that,while the two conditions may conceivably coexistin the same eye or in different members of thesame family, the ICE syndrome and PPD are

distinct entities. It is concluded that ICE andPPD should be diagnosed on corneal signs alone.While the appropriate signs usually can be seen

with the slit-lamp, ESP, by revealing ICE cellsand distinguishing between ICE-bergs and PPDvesicles, will always provide a definitive diagnosiseven in uncertain cases and thus pro-

mote accurate management of patients and theirfamilies.

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16 Sherrard ES, Buckley RJ. The relief mode: new application ofthe corneal specular microscope. Arch Ophthalmol 1982;100:296-300.

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