Brit. Y. Ophthal. (1976) 6o, 532

Subconjunctival and episcleral lipid deposits

F. T. FRAUNFELDER,* A. GARNER, AND T. C. BARRASFrom the External Diseases Unit, Moorfields Eye Hospital, and theDepartment of Pathology, Institute of Ophthalmology, University of London

Biomicroscopical examination of the peripheralbulbar conjunctiva and episcleral tissue, especiallyat the level of the palpebral fissure, commonlyreveals globules of lipid. The globules vary insize from 30-80 ,tm in diameter, although in anyone individual they tend to be fairly uniform, andwere first described by Paliaga (I959) in Italy. Asubsequent report from America (Fraunfelder andHanna, 1975) indicated that the prevalence of thelipid deposits increases with age, over half thepopulation aged 50 years or more in Arkansas beingaffected. The deposits assume two basic patterns:most often multiple globules lie adjacent to bloodvessels but sometimes they occur in small isolatedfoci. Perivascular distribution is six times more

*Visiting Professor, Institute of Ophthalmology, July 1974 toJuly 1975. Present address: Department of Ophthalmology, Uni-versity of Arkansas Medical Center, 4301 West Markham, LittleRock, Arkansas 72201.

Address for reprints: Dr A. Garner, Institute of Ophthalmology,Judd Street, London WCiH 9QS

common on the nasal side and twice as commonon the temporal side when compared with isolatedpatches (Fraunfelder and Hanna, 1975).The purpose of this report is to compare the

prevalence of this entity in Great Britain with thatobserved in the United States of America, toconsider its relationship to arcus senilis of thecornea, and to describe the histopathologicalfeatures.

Patients and methods

From January to July 1975 over iooo randomly selectedoutpatients at Moorfields Eye Hospital drawn fromvarious parts of Britain were examined biomicroscopi-cally for the presence of conjunctival or episcleral lipids.Some were also examined for comeal arcus senilis.Patients who had not spent at least three-quarters oftheir lives in the United Kingdom were excludedfrom the study. Photographs were taken using a Zeissphoto slit lamp and a macro camera as described byBrown (I970). Twenty-eight eye bank eyes were

FIG. I Slit-lamp photograph ofmultiple lipid globules in deepconjunctiva and episclera. x i I

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Subconjunctival and episcleral lipid deposits 533

100

Ji ~ EZMale*Female

50-

CoAqe 0-29 30-39 40-49 50-59 60-69 70-79

FIG. 4 Prevalence of corneal arcus in men and womenat different ages

FIG. 2 Widespread distribution of lipid globules inbulbar conjunctiva of man who had sustained blastinjury to both eyes. x I4

examined histologically, the tissue being fixed in formolsaline and variously stained with haematoxylin andeosin, oil red 0, osmium tetroxide and oc-naphthylamine(OTAN), and by Okamato's method for cholesterol.Carbowax embedding (a water-soluble wax designed toimpregnate tissues without requiring the prior removalof lipid) was also performed on selected specimens.

ResultsClear round globules were seen at varying depthswithin the conjunctiva but predominated in theepiscleral tissue (Fig. i). The deposits were asymp-

75_ Male

U Femole

50-

a

o 25-a

Aqe 0-29 30-39 40-49 50-59 60-69 70+No.patients 104157 60 64 58 48 10896 75 84 58-38

Lipid qlobules 8 4 7 10 23 IS 32 46 43 54 26 14

FIG. 3 Prevalence of subccnjunctival lipid globules inGreat Britain at different ages in men and women

tomatic and, although differing in size from patientto patient, were of uniform diameter in a givenperson. In one patient, who had sustained a blastinjury during the second world war, the wholebulbar conjunctiva of both eyes was filled with lipidglobules (Fig. 2). The youngest person to show thepresence of globules was 21 years old. The pre-valence and severity of the lesion increased linearlyup to the age of 70 years: beyond this age theprevalence declined (Fig. 3). The proportions ofmen and women with conjunctival lipid deposits

FIG. 5 Stained subconjunctival globules in intactenucleated globe showed pronounced uptake of oil red 0(from colour original). x i 8

were not significantly different. The prevalenceof corneal arcus also increased with age in bothsexes (Fig. 4) but without any reduction beyondthe age of 70 years, so that the correlation in indivi-dual cases between the presence of arcus andconjunctival lipid was not statistically significant.

Examination of the subconjunctival globuleswith a dissecting microscope showed a predomi-nantly perivascular distribution, and it was notedthat heat generated by the illuminating sourcecaused them to fuse and lose their discrete sphericalshape. Treatment of the globules at this stage withoil red 0 produced an intense uptake of the dye

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534 British Journal of Ophthalmology

FIG. 6 Frozen section showing"' extracellular lipid deposits adjacent

to conjunctival blood vessels.Oil red 0. x go

by the deposits (Fig. 5). Although frozen andcarbowax-embedded sections were prepared thelipid globules were seldom retained in the mountedpreparation, the rare exceptions showing amorphousfat devoid of any limiting membrane and appar-

ently located within extracellular spaces in theloose connective-tissue of the subconjunctiva andepisclera (Fig. 6). Staining for cholesterol byOkamoto's method on the gross specimen resultedin a blue-black reaction product. Finely particulatelipid which stained with oil red 0 and gave a

brown-black colour in the OTAN procedure was

demonstrable in the sclera in all cases.

FIG. 7 Section showing lipid spacesin conjunctival stroma surrounded

by giant-cell granulomatous reaction.Haematoxylin and eosin. x I85

A biopsy specimen, which had been taken-someyears earlier from the patient demonstrated inFig. 2, examined in routine paraffin-embeddedsections showed fat spaces surrounded by a granu-

lomatous inflammatory reaction (Fig. 7).

DiscussionConjunctival and episcleral lipid globules are easilymissed unless specifically looked for, ideally usingeither direct or indirect retroillumination. Theaggregated globules resemble frog-spawn and occur

most often between the loops of large, tortuous

blood vessels.

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Subconjunctival and episcleral lipid deposits 535

75 -

UUnited States (Arkansas)

50

o 25-

00Age 0-29 30-39 40-49 50-59 60-69 70+

No.patients261578 124 107 106177 204 272 159 280 96-298Lipid globules 12 22 17 26 38 83 78145 97 174 40 188

FIG. 8 Comparative prevalence of subconjunctivallipid globules in Great Britain and United States ofAmerica at different ag3s. (US data from Fraunfelderand Hanna, I975)

The prevalence of the condition shows a clearrelationship with age. Beyond the age of 70 years,however, the American data show that the rise inprevalence is halted (Fraunfelder and Hanna,1975), while the present study suggests that itmight even be reversed. The American study alsoshowed a preponderance of women with subcon-junctival lipid at all ages, but there was no convinc-ing evidence of such a predilection in Britishsubjects. However, the overall prevalence seemsto be slightly higher in Arkansas (Fig. 8).With increasing age lipid accumulates between

the collagen fibres of the sclera, particularly to-wards the uveal surface, and this process mayshare a common pathogenesis with corneal arcusformation, with which it is commonly associated(Yanoff and Fine, 1975). Consequently, if thesubconjunctival globules originate from the samesource as those in the sclera-and our finding ofscleral lipid deposition in all eyes with conjunctivalglobules examined histologically lends some sup-port to this hypothesis-a good correlation betweenthe conjunctival lesion and corneal arcus mightalso have been expected. This, however, was notthe case.The reason for this disparity is not immediately

obvious but may be linked with the observationthat the lipid deposited in the cornea and sclerais in a finely particulate form, being largely boundto low density lipoprotein (Walton, I973), whereas

that in the loose stroma of the conjunctiva occursas much larger globules which probably representunbound fat. There is good evidence that the lipidof corneal arcus senilis is derived from the circu-lating plasma (Cogan and Kuwabara, I959;Walton, I973; Walton and Dunkerley, I974), andthe frequent perivascular and extracellular locationof the deposits as well as their cholesterol contentare conducive to similar reasoning in respect ofthe conjunctival lesion. Whether or not the loosestructure of the subconjunctival stroma facilitatesthe fusion of smaller lipid particles, which haveseeped through a vascular endothelium subject toan age-related increase in permeability, is notknown.

Other possibilities for the origin of the conjunc-tival globules, referred to in an earlier paper(Fraunfelder and Hanna, 1975), include forwardmigration of orbital fat, degenerative changes inthe tissues, and trauma to the conjunctival bloodvessels caused by eye movements and blinking.The essentially extracellular location of the lipiddroplets, however, lends little support to any butthe last of these suggestions. The extent to whichleakage of circulating fat might represent a funda-mental degenerative change in the conjunctivalvessels, after the manner postulated for arterio-sclerosis in other sites, or be attributable to repeatedepisodes of minor trauma is not known, althoughthe finding of massive lipid deposition in the con-junctiva of a man subjected to blast injury suggeststhat the latter hypothesis is a real possibility.

Fortunately, in view of their high prevalence,conjunctival and anterior episcleral lipid globulesalmost never give rise to symptoms-the extremelyrare exception appearing to be a granulomatousreaction which probably reflects an alteration inthe nature of the fat.

SummaryBiomicroscopical examination of the bulbar con-junctiva and anterior episclera of iooo randomlyselected outpatients showed the presence ofmultiple discrete lipid globules in 30 per cent. Thelipid deposits were asymptomatic. Their prevalencewas age-related, while their distribution andcomposition were consistent with origin from theconjunctival blood vessels.

ReferencesBROWN, N. A. (I970) Brit. J3. Ophthal., 54, 697COGAN, D. G., and KUWABARA, T. (195o) Arch. Ophthal., 73, 553FRAUNFELDER, F. T., and HANNA, C. (I975) Amer. J3. Ophthal., 79, 262PALIAGA, G. P. (I959) Boll. Oculist., 38, 867WALTON, K. W. (1973) Y. Path., III, 263

, and DUNKERLEY, D. J. (1974) Ibid., 114, 217YANOFF, M., and FINE, B. S. (1975) 'Ocular Pathology: a text and atlas', p. 28I. Harper & Row, Maryland

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