British Journal of Ophthalmology, 1988, 72, T3-188

Corneal elastosis within lattice dystrophy lesionsJACOB PE'ER,' BEN S FINE,2 ANITA DIXON,3 AND DAVID S ROTHBERG4

From the 'Department of Ophthalmology, Hadassah University Hospital, Jerusalem, Israel, 2Department ofOphthalmic Pathology, Armed Forces Institute of Pathology, Washington, DC, and the Departments of3Pathology and 4Ophthalmology, Veterans Administration Hospital, Kansas City, Missouri, USA

SUMMARY Corneal buttons oftwo patients with lattice corneal dystrophy were studied by light andelectron microscopy. They showed elastotic degeneration within the amyloid deposits. Theamyloid deposits displayed characteristic staining; the elastotic material (elastin) within thedeposits stained positive with Verhoeff-van Gieson and Movat pentachrome stains and showedautofluorescence. The characteristic ultrastructural findings of amyloid and elastotic material werealso demonstrated. The possibility of the associations of these two materials in the cornea isdiscussed.

Corneal elastosis, also known by a wide variety ofsynonyms," may be seen as a single corneal or ocularfinding, or in association with a variety of chronicocular and corneal disorders such as scarring second-ary to chemical or mechanical trauma, glaucoma,actinic lesions, old inflammation, corneal oedema,conjunctival carcinoma in situ or invasive squamouscell carcinoma, and ochronosis.7I Corneal elastosishas been described in association with lattice cornealdystrophy in a few previous reports.2 "' In one ofthese cases the elastosis was in close relation to theamyloid,"' and in two cases the elastosis was foundwithin the amyloid."9 In the last two there was nodetailed description.The subjects of this report are two patients with

lattice corneal dystrophy in whose corneas we foundelastosis within the amyloid deposits. This findingwas demonstrated by light and electron microscopyand by an autofluorescent technique.

Case reports

CASE 1A 63-year-old white male had a 15-year history ofdecreasing visual acuity in both eyes because ofcorneal opacities that became worse in the fourmonths before his operation. Cataracts had pro-gressed rapidly in the previous six months.There was no known family history of any eye

Correspondence to Jacob Pe'er, MD, Department of Ophthal-mology, Hadassah Urfiversity Hospital, PO Box 12000, 91120Jerusalem, Israel.

disease other than myopia. The patient was admittedto hospital in January 1983 for examination of a lungnodule, but, because he refused bronchoscopy, adefinite diagnosis was not made. There was history ofalcohol abuse in the past, but that had been stoppedfor several months.

In February 1983 the patient was admitted tohospital for penetrating keratoplasty of the right eye,cataract extraction, and posterior chamber lensimplantation. Examination of the eyes revealedvisual acuity of hand motion in each eye. Theintraocular pressures were within normal limits. The

rig. Lcuse 1. Algnt eye snows semiuruansucentdichotomous refractile lines andsome white dots in thecornea.

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Fig. 2 Case 1. Histological section ofthe cornea showsuneven epithelium, fibroticpannus and replacement ofBowman's membrane byfibrous tissue, and basophilichyaline nodules. In the stroma there arefusiform deposits ofamyloid, with hyaline deposits within them. Haematoxylin-eosin.

pupils reacted normally to light. Slit-lamp examina-tion revealed many semitranslucent, dichotomous,refractile lines and some white dots in both corneasconsistent with lattice corneal dystrophy (Fig. 1).There were small pterygia in both eyes. The anteriorchambers were deep and clear. Funduscopic exami-nation could not be done owing to the densecataracts. Ultrasonographic examination wasnormal. After the planned surgical procedure wasperformed, the patient did well, his vision being 6/120without correction in the right eye, corrected to 6/24with pinhole. The graft remained clear.

Pathological findings. Macroscopic examination

Fig. 3 Case 1. The amyloidfusiform materialshowsbirefringence with polarised light, while the hyaline depositswithin itdo notshow this. Congo-red, polarised light.

Fig. 4 Case 1. Black elastotic material within the amyloiddeposits. Verhoeff-van Gieson.

revealed two pieces of tissue. One was labelledpterygium of the right eye and consisted of a singlefragment of grey-brown soft tissue, measuring3x2x2 mm. The entire specimen was submitted forlight microscopic examination. The other piece oftissue was a translucent corneal button, 7 mm indiameter, with many semitranslucent lines in itsstroma. A section of the cornea was submitted forelectron microscopy, while the remainder was sub-mitted for light microscopy.

Microscopic examination of the soft tissuerevealed conjunctiva with focal squamous meta-plasia, hyalinisation and elastotic degeneration ofcollagen, and some chronic inflammation, an appear-ance consistent with pterygium.

Microscopic examination of the cornea revealeduneven epithelium, fibrotic pannus in one area, andreplacement of Bowman's membrane by fibroustissue and basophilic hyaline nodules in some areas(Fig. 2). In the anterior two-thirds of the stroma there

Fig. 5 Case 1. The elastotic material shows strongautofluorescence. Autofluorescence.

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Corneal elastosis within lattice dystrophy lesions

Fig. 6 Case 1. Ultrastructurally the amyloid material (lighter) shows delicatefibrils, mostly non-branching, withoutperiodicity. The elastotic material is electron-dense with irregular edges, showing delicatefibrillar pattern. Electronmicrograph.

were fusiform deposits, stained pink with haema-toxylin and eosin (H and E), displacing collagenlamellae. Within many of these fusiform depositsthere were blue-grey hyaline deposits with irregularborders similar to those found in Bowman's mem-brane and the anterior stromal areas (Fig. 2). Theintervening stroma appeared normal except for someareas of stromal oedema. Descemet's membrane wasunremarkable, and the endothelial cells were attenu-ated. The fusiform deposits were stained deep purplewith periodic acid-Schiff (PAS), red-purple withMasson's trichrome stain, pink-purple with Movat

pentachrome stain, and yellow-grey with Verhoeff-van Gieson (VVG) elastin stain. Congo red stainedthe deposits orange; it showed dichroism of greenand red and birefringence with polarised light, morethan the surrounding stroma and consistent withamyloid material. The hyaline deposits within theamyloid did not show these appearances (Fig. 3). Thehyaline deposits were stained pink-grey with PAS,blue-purple with Masson trichrome, blue-grey withCongo red, and black with VVG and Movat penta-chrome stains, consistent with elastotic material (Fig.4). Von Kossa stain for calcium was negative. These

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deposits were autofluorescent with ultraviolet light(Fig. 5).

Ultrastructurally the amyloid lesions showeddelicate, mostly non-branching fibrils withoutperiodicity, many of them highly aligned. Within thismaterial there were electron-dense deposits withirregular edges consistent with elastin-like materialand showing a delicate fibrillar pattern thatresembled the amyloid pattern (Fig. 6).

CASE 2A 49-year-old Asian Indian male known to havetuberculoid leprosy had suffered for the last fouryears a gradual, slowly progressive diminution ofvision in both eyes. He gave a history of injury with agrass plant to the right eye four years previously. Hisgeneral condition was good. There was no familyhistory of eye disease. On examination his visualacuity was 4/60 in the right eye and 6/60 in the left eye,with intraocular pressure within normal limits. Slit-lamp examination showed typical lattice cornealdystrophy lines in both eyes. In February 1983 heunderwent penetrating keratoplasty of his right eye,with a graft of 7-5 mm in diameter.

Pathological findings. Macroscopic examinationrevealed a yellowish corneal button 7-5 mm indiameter with semi-translucent lines in its stroma.The endothelial surface was covered with pigmentednodules. A section of the cornea was submitted forelectron microscopy, while the remainder was sub-mitted for light microscopy.

Microscopic examination revealed uneven cornealepithelium. Bowman's membrane was replaced inareas by fibrotic connective tissue and small foci ofhyaline elastotic nodules. There were fusiformdeposits all over the stroma, stained pink withH and E, displacing collagen lamellae. Within someof the fusiform deposits there were basophilic hyalinedeposits with irregular borders similar to those foundin Bowman's membrane and anterior stromal areas.The intervening stroma appeared normal.Descemet's membrane was unremarkable. Theendothelial cells were mildly attenuated. Theposterior surface of the cornea was severely over-grown with a pigmented fungus which we interpretedas a contaminant. Special stains gave the same resultsas in case 1. The fusiform deposits were stainedorange with Congo red and showed dichroism andbirefringence with polarised light more than thesurrounding stroma, consistent with amyloidmaterial. The hyaline deposits within them did notshow these appearances. They stained black withVVG and Movat pentachrome stains (Fig. 7) andwere autofluorescent with ultraviolet light, consistentwith elastotic material.

Ultrastructurally the amyloid lesions showed

Fig. 7 Case2. Fusiform amyloid depositin thestroma withelastotic material stained black within it. Movatpentachrome.

delicate, mostly non-branching fibrils withoutperiodicity. Within this material there were electron-dense deposits with irregular edges consistent withelastin-like material, the same findings as in case 1(Fig. 8).Discussion

The clinical and histological findings in our casesare compatible with lattice dystrophy of the cornea.The lack of family history does not rule out thispossibility. Although lattice dystrophy has anautosomal dominant pattern of inheritance, it doesnot present in all affected members of families withthe disease. The subtle expression of the genereduces the number of detected individuals to about10-25% in some families." 12The genesis of amyloid deposition elsewhere in the

body as well as in the cornea is not well understood.Two main hypotheses about the origin of amyloid inlattice dystrophy are: (1) collagen degenerationcaused by lysosomal enzymes released fromabnormal keratocytes,'2'4 and (2) synthesis ofamyloid by keratocytes.'2 '5 Other theories considerthe lattice as focal amyloidosis restricted to thecornea,'6 as primary degeneration of cornealnerves,'7 or as related to amyloid protein AA, aprecursor protein possibly attached to a transportprotein.The current concept of the pathogenesis of corneal

elastosis is that it is a result of collagen fibredegeneration.79' 20 The resistance of the elastoticmaterial to digestion with elastase"' and its auto-fluorescent characteristic show its differences fromelastin and its similarity to elastotic degenerationelsewhere, as in the conjunctiva. Another study,based on some tinctorial dissimilarities between

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187Corneal elastosis within lattice dystrophy lesions

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Fig. 8 Case 2. Ultrastructurally the amyloid material (lighter) is composed ofdelicate, mostly non-branchingfibrils withoutperiodicity. The elastotic material is electron-dense, with irregular borders, showing delicatefibrillar pattern. Electronmicrograph.

pseudoelastic fibres in pingueculae and spheroidalelastotic deposits in the cornea, suggests that thespheroidal elastotic deposits might be a composite ofdegenerate collagen and a second non-collagenous

protein." The latter may be of altered plasmaconstituents from leaking limbal vessels.22The accepted theories of collagen degeneration in

both lattice dystrophy and corneal elastosis suggest

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the possibility of a closely related metabolic reasonfor both, although one is genetically inherited and theother is not. Corneal elastosis may be associated witha variety of chronic ocular and corneal disorders.7"Our patients presented clinical findings or a history ofother corneal diseases like those of other cases withcorneal elastosis. Case 1 had pterygium in both eyes.The main characteristic of pterygium is elastoticdegeneration of the conjunctival collagen fibres, andcases of pterygium also sometimes show elastoticdegeneration of the cornea. Case 2 presented ahistory of old trauma to the cornea, a commonfeature of other cases of elastotic degeneration. Wecan conclude that in these two cases of latticedystrophy there were other causes of the elastoticdegeneration. The combined finding of latticedystrophy and elastosis was described in previousreports,2 1'" so our earlier explanations can accountfor this combination but not the existence of theelastotic material within the amyloid, as in our cases.

The opinions or assertions contained herein are the private views ofthe authors and are not to be construed as official or as reflecting theviews of the Department of the Army or the Department ofDefense.

References

1 Freedman A. Labrador keratopathy. Arch Ophthalmnol 1965; 74:198-202.

2 Garner A. Keratinoid corneal degeneration. Br J Ophthaltnol1970; 54: 769-80.

3 Klintworth G. Chronic actinic keratopathy. Am J Pathol 1972;67: 327-42.

4 Fraunfelder FT, Hanna C, Parker JM. Spheroid degeneration ofcornea and conjunctiva. 1. Clinical course and characteristics.Am J Ophthalmol 1972; 74: 821-8.

5 Fraunfelder FT, Hanna C, Parker JM. Spheroid degeneration ofcornea and conjunctiva. 2. Pathology. Amn J Ophthalmol 1972;74: 829-39.

6 Freedman A. Climatic droplet keratopathy. 1. Clinical aspects.A rc/i Ophthalmol 1973; 89: 193-7.

7 Brownstein S, Rodrigues MM, Fine BS, Albert AN. Theelastotic nature of hyaline corneal deposits. Amn J Ophthalmol1973;75:799-809.

8 Fraunfelder FT. Hanna C. Spheroidal degeneration of corneaand conjunctiva. 3. Incidences, classification and etiology. Am JOphthalmol 1973; 76: 41-5(0.

9 Rodrigues MM, Laibson PR, Weinreb S. Corneal elastosis. ArchOphthalmol 1975; 93: 111 -4.

1t) Dubord PJ, Rodrigues MM, Krachmer JH. Corneal elastosis inlattice corneal dystrophy. Ophthalmology 1981; 88: 1239-43.

11 Ramsey RM. Familial corneal dystrophy lattice type. Trans AmnOphthalmol Soc 1957; 60: 701-39.

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13 Klintworth GK. Current concepts on the ultrastructural patho-genesis of macular and lattice corneal dystrophies. Birth Defects(Orig Art Ser) 1971; 7: 27-31.

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Acceptedfor publication 30 December 1986.

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