British Journal of Ophthalmology, 1986, 70, 126-131 Scrolls of Descemet's membrane as unusual giant nodules on the posterior cornea: histochemical and ultrastructural findings R A ALEXANDER AND A H S RAHI From the Department of Pathology, Institute of Ophthalmology (University of London), 17/25 Cayton Street, London EC] V 9A T SUMMARY Unusual giant nodules on the posterior surface of Descemet's membrane were observed in two out of over 400 corneae examined during routine histopathological reporting. Both of the patients, a 60-year-old man and a 26-year-old woman, had histories of corneal trauma. Neither was associated with chronic keratitis or corneal dystrophy. Light microscopy showed these nodules to be composed of material resembling Descemet's membrane. Histochemical and electron microscopical preparations identified oxytalan fibres within the outer layers of the nodules. These fibres are not a feature of the normal adult Descemet's membrane. The findings are discussed and compared with other nodular lesions of Descemet's membrane. Descemet's membrane is an apparently homo- geneous structure that is produced by the corneal endothelium. Electron microscopy, however, has shown that it consists of two distinct layers-an anterior, organised banded zone and a posterior, relatively unorganised, non-banded zone that increases in thickness with age.'2 Small islands of 100 nm wide-spacing collagen may be observed within the periphery of the posterior layer.3 Hassal- Henle warts are focal thickenings on the posterior surface of the peripheral Descemet's membrane; they are considered to be related to aging.34 Similar nodular thickenings in the central cornea are a feature of Fuchs's late hereditary endothelial dystrophy, while focal fusiform nodular swellings are seen in posterior polymorphous dystrophy.' Recently Scattergood et al.6 described giant nodules that consisted of scrolls of Descemet's membrane in a patient with syphilitic interstitual keratitis. If Descemet's membrane ruptures, the severed edges tend to roll posteriorly as if under a state of tension. This elastic property of Descemet's mem- brane is well known, though typical elastic fibres have not been demonstrated within it.2 5 However, Heathcote et al.' biochemically identified desmosine and isodesmosine in bovine Descemet's membrane. Correspondence to Mr R A Alexander. These lysine-derived amino acids are considered to be unique to elastin.6' The mature elastic fibre is composed of two morphologically and biochemically different elements:"" a central amorphous elastin core, which may amount to 90% or more of the fibre volume, and a predominantly peripheral array of 10-16 nm diameter, tubular appearing, microfibrils, Oxytalan fibres" exist as bundles of the glycoprotein micro- tubules alone. They correspond to the earliest identi- fiable stage of elastogenesis.'2 Elaunin fibres,'3 the third member of the elastic fibre system, represent an intermediate stage of development between oxytalan and mature elastic, being seen as bundles of micro- tubules with infiltrating islands of amorphous material. '4 The histochemical properties of the elastic fibre family are outlined in Table 1. As with mature elastic, neither oxytalan nor elaunin fibres are demonstrable in the normal adult human cornea.7 Oxytalan fibres though, have been observed as a transient feature of the young Descemet's membrane of man' and cat."' They have also been identified within the retrocorneal fibrous tissue layer produced by endothelial cells in examples of Fuchs's endothelial dystrophy,'6 1' congenital endothelial dystrophy, 16 posterior polymorphous dystrophy,'6 and advanced keratoconus.'8 The pro- duction of oxytalan fibres in later life, as seen in these 126 on May 22, 2020 by guest. Protected by copyright. http://bjo.bmj.com/ Br J Ophthalmol: first published as 10.1136/bjo.70.2.126 on 1 February 1986. Downloaded from
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British Journal of Ophthalmology, 1986, 70, 126-131
Scrolls of Descemet's membrane as unusual giantnodules on the posterior cornea: histochemical andultrastructural findingsR A ALEXANDER AND A H S RAHI
From the Department of Pathology, Institute of Ophthalmology (University of London), 17/25 Cayton Street,London EC]V 9A T
SUMMARY Unusual giant nodules on the posterior surface of Descemet's membrane wereobserved in two out ofover 400 corneae examined during routine histopathological reporting. Bothof the patients, a 60-year-old man and a 26-year-old woman, had histories of corneal trauma.Neither was associated with chronic keratitis or corneal dystrophy. Light microscopy showed thesenodules to be composed of material resembling Descemet's membrane. Histochemical andelectron microscopical preparations identified oxytalan fibres within the outer layers of thenodules. These fibres are not a feature of the normal adult Descemet's membrane. The findings arediscussed and compared with other nodular lesions of Descemet's membrane.
Descemet's membrane is an apparently homo-geneous structure that is produced by the cornealendothelium. Electron microscopy, however, hasshown that it consists of two distinct layers-ananterior, organised banded zone and a posterior,relatively unorganised, non-banded zone thatincreases in thickness with age.'2 Small islands of100 nm wide-spacing collagen may be observedwithin the periphery of the posterior layer.3 Hassal-Henle warts are focal thickenings on the posteriorsurface of the peripheral Descemet's membrane;they are considered to be related to aging.34 Similarnodular thickenings in the central cornea are afeature of Fuchs's late hereditary endothelialdystrophy, while focal fusiform nodular swellings areseen in posterior polymorphous dystrophy.' RecentlyScattergood et al.6 described giant nodules thatconsisted of scrolls of Descemet's membrane in apatient with syphilitic interstitual keratitis.
If Descemet's membrane ruptures, the severededges tend to roll posteriorly as if under a state oftension. This elastic property of Descemet's mem-brane is well known, though typical elastic fibres havenot been demonstrated within it.2 5 However,Heathcote et al.' biochemically identified desmosineand isodesmosine in bovine Descemet's membrane.
Correspondence to Mr R A Alexander.
These lysine-derived amino acids are considered tobe unique to elastin.6'The mature elastic fibre is composed of two
morphologically and biochemically differentelements:"" a central amorphous elastin core, whichmay amount to 90% or more of the fibre volume, anda predominantly peripheral array of 10-16 nmdiameter, tubular appearing, microfibrils, Oxytalanfibres" exist as bundles of the glycoprotein micro-tubules alone. They correspond to the earliest identi-fiable stage of elastogenesis.'2 Elaunin fibres,'3 thethird member of the elastic fibre system, represent anintermediate stage of development between oxytalanand mature elastic, being seen as bundles of micro-tubules with infiltrating islands of amorphousmaterial. '4 The histochemical properties of the elasticfibre family are outlined in Table 1.As with mature elastic, neither oxytalan nor
elaunin fibres are demonstrable in the normal adulthuman cornea.7 Oxytalan fibres though, have beenobserved as a transient feature of the youngDescemet's membrane of man' and cat."' They havealso been identified within the retrocorneal fibroustissue layer produced by endothelial cells in examplesof Fuchs's endothelial dystrophy,'6 1' congenitalendothelial dystrophy, 16 posterior polymorphousdystrophy,'6 and advanced keratoconus.'8 The pro-duction of oxytalan fibres in later life, as seen in these
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Table 1 Summary ofthe histochemical properties ofoxytalan, elaunin, and mature elasticfibres
Fibre type
MatureMethods elastic Elaunin Oxytalan
Verhoeff iron haematoxylin + - -Ox-Verhoeff iron haematoxylin +Gomori aldehyde fuchsin + +Ox-aldehyde fuchsin + + +Elastase-Verhoeff iron haematoxylin AElastase-Aldehyde fuchsin A AElastase-ox-aldehyde fuchsin A S* SOx-elastase-aldehyde fuchsin A A A
Ox=section oxidation in 10% Caroat. - =unstained. + =stained.S=stained (little or no change). A=abolished staining.*Staining ofamorphous core abolished by elastase but peripheralmicrofibrils induced to stain by oxidation.
corneal diseases, may be the result of derepression offetal genes.
In a review of more than 100 corneal discs and over300 eyes which were removed for a variety of reasonswe found two examples of giant nodules on theposterior surface of Descemet's membrane whichwere morphologically similar to those of Scattergoodet al.6The present communication describes the distribu-
tion of elastic related fibres in our two cases with giantnodules of Descemet's membrane. The findings arecompared with those of other nodular lesions ofDescemet's.
Materials and methods
Specimen 1 was an eye enucleated for malignantmelanoma of the choroid. The patient was a 60-year-old man who had a history of perforating injury to thecornea during childhood.Specimen 2 was an eye from a 26-year-old woman.
It was painful and blind as a consequence of long-standing raised intraocular pressure (congenitalglaucoma). There was evidence of previousiridectomy.
Neither of the patients had clinical evidence ofeither corneal dystrophy or chronic keratitis.
LIGHT MICROSCOPYBoth eyes were fixed in 10% formal saline, processedinto paraffin wax, and sectioned at a thickness of6 Rm.
Sections were dewaxed, hydrated, and stained bythe following methods:Mayer's haematoxylin and eosin for routine
examination.Verhoeff's iron haematoxylin for mature elastic
fibres.
Gomori's aldehyde fuchsin for elaunin and matureelastic fibres.Aldehyde fuchsin following oxidation in 10%
caroat for 60 min or peracetic acid for 30 min'9 todemonstrate oxytalan fibres in addition to elauninand elastic. Oxytalan fibres are identified histo-chemically by the fact that they stain with aldehydefuchsin only when tissue sections have been pre-viously exposed to a strong oxidising agent." 1219(Caroat, active component potassium peroxymono-sulphate, was obtained from Degussa Ltd, CheadleHulme, Cheshire.)
Gomori's silver impregnation method for reticularfibres.
Gomori's one step trichrome for collagen.McManus periodic acid Schiff sequence.
TRANSMISSION ELECTRON MICROSCOPYOne of the two nodules on the posterior cornea ofcase 2 was excised from the wax block, dewaxed,rehydrated, and postfixed in 1% osmium tetroxide inPalade buffer at pH 7*4. The specimen was subse-quently processed and embedded in Araldite. Thinsections were stained by alcoholic uranyl acetate andlead citrate and studied under a Joel 100C electronmicroscope.
Results
CASE 1The most significant abnormality was the presence ofa giant dome-shaped nodule on the posterior surfaceof the central cornea. It measured approximately0-4x0.19 mm in cross section. The central corneaalso showed signs of previous perforating injury, suchas deficiencies of Bowman's zone, disorganisation ofthe stromal lamallae, and fragmentation ofDescemet's membrane. The basal or stromal aspectof the nodule was seen to be composed of fibrous scartissue which had penetrated through the break inDescemet's membrane. The 'new Descemet's mem-brane' which covered the scar tissue and constitutedthe giant nodule was greatly thickened, in contrast tothe old Descemet's membrane with which it wascontinuous. A few small guttate excrescences orwarts were seen immediately to one side of thenodule.Many oxytalan fibres were identified within the
posterior or outer layers of the thickened Descemet'smembrane/nodule. These fibres outlined severalburied and hence unsuspected warts within thenodule in addition to those previously observed.Where oxytalan fibres penetrated between individualwarts they imparted a fern leaf pattern to the nodule.Oxytalan fibres as well as presenting as distinct fibreswere also seen as dots. This appearance was interpre-
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ted as being fibres cut in cross section and henceencircling the warts in the nodule. Oxytalan was notobserved in the more anterior or inner layers of thenodule. A relatively small number of oxytalan fibreswere seen immediately beneath the endotheliumover most of Descemet's membrane. A few very fineoxytalan fibres were present beneath the basal cells ofthe central corneal epithelium and superficial stromain the region of the old perforating wound.
Elaunin and mature elastic fibres were not identi-fied within any part of the cornea. The severed endsof the original Descemet's membrane observedwithin the nodule were, however, weakly stained bythe Verhoeff elastic method, but not by aldehydefuchsin-with or without preliminary oxidation.
Argyrophillic reticular fibres were shown by the
Fig. 1 One ofthe giant nodulesfrom case 2. The severed and coiledDescement's membrane is seenwithin the nodule. Fine oxytalanfibres (arrows) are only seen withinthe more posterior or outer regionsofthe nodule. Thesefibres outlineunsuspected guttate excresences (g).(Oxidation-aldehydefuchsin,x544). Inset. Ifthe oxidation stepofthe technique is omitted, oxytalanfibres fail to stain. Elaunin andelasticfibres are notpresent.(Aldehydefuchsin, xJ36).
Gomori silver method to give the nodule andDescemet's membrane a multilayered appearance.Reticular fibres were present in the anterior layers ofthe nodule as well as within the oxytalan-containingposterior layers. As with oxytalan, some reticularfibres were considered to encircle the guttateexcrescences.
CASE 2Two large nodules were seen to project from theposterior surface of the cornea. The nodulesappeared to be formed by the infolding of a greatlythickened Descemet's membrane. The centre of bothnodules contained severed and spiraled fragments ofthe original Descemet's membrane. The two largenodules measured 0 14x0 2 mm and 0-2x0 1 mm in
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cross section. The posterior surface of Descemet'smembrane on either side of the nodules had occa-sional small focal swellings or guttate excrescences.A great many fine oxytalan fibres were identified
within the more posterior-outer layers of the thick-ened Descemet's membrane which constituted thegiant nodules (Figs. 1 and 2). The oxytalan fibrestaining outlined and so revealed numerous buriedindividual and multiple unsuspected guttate wartswithin the nodules. The excrescences of Descemet'smembrane proper were also outlined by oxytalanfibres. Oxytalan fibres were not present within theanterior-inner layers of the nodules. A small numberof very fine fibres were demonstrated beneath thecorneal epithelium and within the superficialstroma.
Elaunin and elastic fibres were not seen within thecornea. However, as with case 1, the coiled, severedends of Descemet's membrane within the noduleswere weakly stained by the Verhoeff technique butnot by the aldehyde fuchsin methods.
Argyrophilic reticular fibre staining gave a multi-laminar appearance to both the normal Descemet'smembrane and the nodules.Transmission electron microscopy of the giant
nodule shown in Fig. 1 revealed four morphologicallydifferent layers or zones. The first two layers, at thecentre of the nodule, were formed from the anteriorbanded and posterior non-banded zones of thecoiled, severed ends of Descemet's membrane.The third layer, which formed the bulk of the noduleand the buried excrescences, resembled the bandedzone of Descemet's membrane proper. In addition itcontained fine fibrils and basement membrane orground substance material. This latter material cor-
responds to the reticular fibres seen by light micro-scopy. The fourth and outermost layer (Fig. 3)appeared less compact than the others and was ofvariable thickness. It was seen to fill the spacesbetween and around the individual excrescences togive a smooth outline to the nodule. This loosefibrous layer consisted of collagen fibrils, reticularfibres, and bundles of 12 nm diameter microtubulescharacteristic of oxytalan. Oxytalan fibres werenot observed in the other zones of the nodule.The absence of elaunin and elastic fibres was con-firmed.
Discussion
Oxytalan fibres have been identified in several con-ditions of the cornea associated with thickening ofDescemet's membrane."s In congenital hereditaryendothelial dystrophy Descemet's membrane is uni-formly thickened by the production of a fibrillarcollagenous layer posterior to the membraneproper."' In addition to possessing collagen andbasement membrane material the layer shows a greatmany randomly orientated oxytalan fibres.'6 Like-wise Descemet's membrane of the central corneamay be thickened in cases of advanced keratoconus.The retrocorneal fibrous membrane shows manyroughly parallel oxytalan fibres lying at approxi-mately 800 to the posterior surface of Descemet'smembrane.'8 In posterior polymorphous dystrophythe abnormal posterior fibrous layers form discretefusiform nodular swellings.' Oxytalan fibres arepresent within this tissue and are seen to outline theposterior surfaces of the swellings.'6 They are notapparent within the nodules or elsewhere in
Fig. 2 The othergiantnodulefrom case2. Oxytalanfibres(arrows) reveal multipleguttae (g)within the outer aspects ofthenodule. (Oxidation-aldehydefuchsin, x436).
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Descemet's membrane. 6 Certain disease states, mostnotably Fuchs's endothelial dystrophy, show manydome or mushroom shaped guttate excrescencesalong the posterior surface of a thickened Descemet'smembrane.52'' Iwamoto and DeVoe2' showed thatthe thickened membrane consisted of up to fivedifferent collagenous layers: the anterior banded and
posterior non-banded zones of Descemet's mem-brane; a posterior banded layer which also formedthe warts; a border region containing 'thin fibrils' inaddition to wide-spacing collagen, collagen fibrils,and basement membrane material; and a fibrillarlayer similar to the border layer but which did notshow wide-spacing collagen. Oxytalan fibres are
ri'g. Eelectron micrograph showingpart ofthe loosefibrous outermost layer of the noduleshown in Fig.1. Numerous oxytalanfibres (arrows), composed ofaligned 12 nm diameterfibrils are seen. Some ofthese'islands' ofoxytalan probably representsuccessive sightings ofthesame longfibre. Small diameter collagenfibrils (c) are mainly shown as cross-sectioned 'dots'. Basement membrane or reticularfibres (r) are alsopresent. (Uranyl acetate-lead citrate, x37500).
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present in large amounts within both the border andfibrillar layers of the retrocorneal collagenousmembrane.'617 Oxytalan thus outlined the warts butwas not present within them. Significant numbers ofoxytalan fibres lay parallel to the surface ofDescemet's membrane, where they encircled indi-vidual excrescences.'7 Reticular fibres (basementmembrane material) were present within theposterior banded layer as well as the two layerscontaining oxytalan fibres.'7 Similar warts commonlyoccur in small numbers on the peripheral cornea(Hassal-Henle bodies) or over the central cornea as apart of normal endothelial aging.34 Oxytalan fibresare present in small numbers over the posteriorsurface only of most Hassal-Henle warts.7
If the giant nodules of our study could be unfoldedand flattened, then on ultrastructural morphologyand oxytalan fibre staining they would most closelyresemble the posterior structures of Fuchs's endo-thelial dystrophy. However, case 1, a 60-year-old,did not have guttate excrescences on the centralcornea unassociated with the nodule. Case 2, a 26-year-old, did have a small number of warts scatteredover Descemet's membrane and therefore couldconceivably be an early example of Fuchs'sdystrophy. It is interesting that the nodules ofboth cases should contain increased numbers ofexcrescences as compared with the rest ofDescemet's membrane.To the best of our knowledge this report is the first
detailed documentation of the fibrous tissue nature ofgiant nodules of Descemet's membrane. There wasno sex or age predilection, but both patients had ahistory of corneal injury resulting in a transientlowering of intraocular pressure. Since wrinkles andfolds in Descemet's membrane are constantfeatures of ocular hypotony,22 23 it is conceivable thatsuch folds may have developed in the cases underdiscussion. These folds may have been maintainedfor a considerable time, resulting in altered endo-thelial activity and overproduction of connectivetissues, thus forming the giant nodules.Multilaminar thickenings of Descemet's mem-
brane, secondary focal guttae, and retrocornealhyaline ridges have been observed in patients withinterstitial keratitis,20 and scrolls of Descemet's mem-brane forming giant nodules have been reported inone case.6 Neither of our cases had clinical orhistological evidence of interstitial keratitis, andtherefore such giant nodules of Descemet's mem-brane do not appear to be pathognomonic of inter-stitial keratitis.
References
I Fine BS, Yanoff M. Ocular histology. A text and atlas. NewYork: Harper and Row, 1972.
2 Tripathi RC. Fine structure of mesodermal tissues of the humaneye. Trans Ophthalmol Soc UK 1974; 94: 663-95.
3 Feeney ML, Garron LK. Descemet's membrane in the humanperipheral cornea. In: Smelser GK, ed. The structure of the eye.New York: Academic Press, 1961: 367-80.
4 Lorenzetti DW, Uotila MH, Parikh RN, Kaufman HE. Centralcornea guttata. Incidence in the general population. Am JOphthalmol 1967; 64: 1155-967.
5 Klintworth GK. The cornea-structure and macromolecules inhealth and disease. A review. Am J Pathol 1977; 89: 718-808.
6 Scattergood KD, Green WR, Hirst LW. Scrolls of Descemet'smembrane in healed syphilitic interstitial keratitis.Ophthalmology (Rochester) 1983; 90: 1518-23.
7 Alexander RA, Garner A. Elastic and precursor fibres in thenormal human eye. Exp Eye Res 1983; 36: 305-15.
8 Heathcote JG, Eyre DR, Cross J. Mature bovine Descemet'smembrane contains desmosine and isodesmosine. BiochemBiophys Res Comm 1982; 108: 1588-94.
9 Ross R, Bornstein P. The elastic fiber. I. The separation andpartial characterization of its macromolecular components.J Cell Biol 1969; 40: 366-81.
10 Cleary EG, Fanning JC, Prosser 1. Possible roles of microfibrilsin elastogenesis. Connect Tissue Res 1981; 8: 161-6.
11 Fullmer HM, Lillie RD. The oxytalan fibre: a previouslyundescribed connective tissue fibre. J Histochem Cytochem 1958;6: 425-30.
12 Fullmer HM, Sheetz JH, Nakates AJ. Oxytalan connectivetissue fibres: a review. J Oral Pathol 1974; 3: 291-316.
13 Gawlik Z. Morphological and morphochemical properties of theelastic system of the motor organ of man. Folia HistochemCytochem (Krakow) 1965; 3: 233-51.
14 Cotta-Pereira G, Guerra-Rodrigo F, Bittencourt-Sampaio S.Oxytalan, elaunin and elastic fibres in the human skin J InvestDermatol 1976; 66: 143-8.
15 Carrington SD, Alexander RA, Grierson I. Elastic and relatedfibres in the normal cornea and limbus of the domestic cat. J Anat1984;139:319-32.
16 Garner A, Alexander RA. Pre-elastic (oxytalan) fibres incorneal pathology. In: The cornea in health and disease. VIthCongress European Society of Ophthalmology, Brighton 1980.London: Royal Society of Medicine-Academic Press,1981;213-6.
17 Alexander RA, Grierson I, Garner A. Oxytalan fibres in Fuchs'endothelial dystrophy. Arch Ophthalmol 1981; 99: 1622-7.
18 Alexander RA. Elastic and related fibres in the human cornea.M.Phil thesis. University of London, 1981.
19 Alexander RA, Clayton DC, Howes RC, Garner A. The effectof oxidation upon the demonstration of corneal oxytalan fibres-a light and electron microscopical study. Med Lab Sci 1981; 38:91-101.
20 Waring GO, Rodrigues MM, Laibson PR. Corneal dystrophiesII. Endothelial dystrophies. Surv Ophthalmol 1978; 23: 147-68.
21 Iwamoto T, DeVoe AG. Electron microscopic studies on Fuchs'combined dystrophy 1. Posterior portion of the cornea. InvestOphthalmol Vis Sci 1971; 10: 9-28.
22 Moreau, Cornibert, Mugneret. Hypotonie grave par denutri-tion. Bull Soc Ophtalmnol Fr 1963: 243-6.
23 Murthy G, Adrianwala SD. Bilateral Descemet's wrinkles inacute gastro-enteritis. Indian J Ophthalmol 1984; 34: 229-30.
Acceptedfor publication 30 May 1985.
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