British Journal of Ophthalmology, 1989, 73, 900-906

Fundus changes in mesangiocapillaryglomerulonephritis type II: clinical and fluoresceinangiographic findingsJ DUVALL-YOUNG,' C D SHORT,? M F RAINES,' R GOKAL,' ANDW LAWLER'

From the 'Department of Ophthalmology, 'Department of Renal Medicine, and 'Department of Pathology,University of Manchester.

SUMMARY Previously we have demonstrated a deposit in Bruch's membrane in a single case ofmesangiocapillary glomerulonephritis type II. We studied a group of patients with this disease anddescribed extensive clinical and fluorescein angiographic abnormalities, which were in markedcontrast to the findings in a group of patients with other forms of glomerulonephritis. This findingcontributes to our understanding of the pathophysiology of the complex of the retinal pigmentepithelium, Bruch's membrane, and choriocapillaris.

A comparison can be made between the anatomy ofthe glomerulus and the choriocapillaris-Bruch'smembrane-retinal pigment epithelium complex, inwhich the choriocapillaris is likened to the glomerulartuft, Bruch's membrane to the glomerular basementmembrane, and the retinal pigment epithelium to theglomerular epithelium. '

In a previous case report of a patient with type IImesangiocapillary glomerulonephritis (MCGN) wehave demonstrated the occurrence of deposits in thechoriocapillaris and Bruch's membrane which havethe clinical appearance of drusen but the histopatho-logical characteristics of deposits in the glomerulus.'In type II MCGN, which is frequently associatedwith partial lipodystrophy (PLD), deposits ofelectron dense material, often with a ribbon likeappearance, are found within the glomerular base-ment membrane.' This is in contrast to the discretedeposits found in (a) membranous nephropathy,where the material lies initially between the base-ment membrane and the epithelium; (b) in type IMCGN, where the deposit is predominantly sub-endothelial between the basement membrane andthe endothelium; and (c) in mesangial proliferativeglomerulonephritis, where the majority of thedeposits are in the mesangium4 (Fig. 1).We have therefore examined clinically the eyes of

Correspondence to J Duvall-Young, FRCS, Walton Hospital, RiceLane, Liverpool L9 lAE.

patients with a variety of glomerular disorders,including further cases of type II MCGN and partiallipodystrophy (PLD), and report our findings.

Methods and patients

From the diagnostic index at the Manchester RoyalInfirmary Renal Unit we selected for ophthalmicinvestigation 17 patients with biopsy provedglomerular disease and two further patients withPLD but who had never had a renal biopsy. Thehistological diagnosis was withheld from the ophthal-mologists who examined the patients by routineclinical methods, fundus photography, and fundusfluorescein angiography. All the patients werenormotensive and had been so for some months,though many had had a period of hypertensionearlier in the course of their illness. Patients 4, 7, and13 had reached end stage renal failure and had hadsuccessful renal transplantation at the time of thestudy. No patient was receiving dialysis.

Details of the patients are given in Tables 1, 2,and 3.

Results

None of the patients had ocular symptoms. All theanterior segments appeared normal and no hyperten-sive retinopathy was detected.

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901Fundus changes in mesangiocapillary glomerulonephritis type

Fig. I Predominant sites ofdeposition ofimmunoreactiie and electron-dense material in various glomerulopathies.

Of the 12 patients without PLD six had type IMCGN, one had minimal change disease (a termused by renal pathologists to describe a nephritis inwhich there is no evidence of disease on lightmicroscopy), and five had membranous nephropathy.

Table 1 Clinical details of cases with PLD

CaseAge Sex Glomerular Timesince Blood Currentt(yr) disease diagnosis pressure medication

(yr) (mm Hg)

1 43 M MCGN 11 t)6 140/90 TenoreticNifedipineHydralazine

2 45 F MCGN (type 27 135/90 Atenololunknown) Methyldopa

Bendrofluazide3 28 F MCGN 11 24 13(1/80 Cyclosporin

Atenolol4 36 M MCGN II 22 15(1/85 Allopurinol

CaptoprilFrusemide

5 30 F Nephrotic 14 15(1/8(1 Cyclosporinsyndrome: Prednisoloneno biopsy Atenolol

6 43 F No biopsy; 11(1/7(1 Anxiolyticsnormal renalfunction

7 43 M MCGN 11 31 115/7(1 Tenoretic

Tenoretic=atenolol 1(K) mg and chlorthalidone 25 mg.

Ophthalmoscopic examination of these eyes revealeda few drusen (Fig. 2), but with no difference in

Table 2 Clinical details of cases without PLD

CaseAge Sex Glomerular Time since Blood Current(jr) disease Diagnosi.s pressure medication

(yr) (mnn Hg)

8 51 M Membranous 2 180/1(X) PrednisoloneAtenololNifedipine

9 31 M MCGN 1 6 140/90 Nil10 43 F MCGN I 9 140/85 Nil11 44 F MCGN 1 6 16(0/9(0 Azathioprine

PrednisoloneAtenolol

12 73 M Membranous 5 14(0/7(0 Nil13 49 F MCGN I 180/95 Prednisolone

AzathioprineAtenololNifedipine

14 39 M Membranous 6 125/90( B3endrofluazide15 32 M Membranous 2 14(0/90( Prednisolone

FrusemideSpironolactone

16 25 F MCGN I 15 (1((/90( Nil17 501 M MCGN 1 13 16(1/90) Methsldopa

FrusemidePropranolol

18 29 F Minimal 3 90(/60( Nilchange

19) 1() F Membranous 7 30/8(1 Nil

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J Duvall-Young, CD Short, M FRaines, R Gokal, and W Lawler

Table 3 Summary ofpatients

With partial lipo(dvstrophv Without partial lipodystroph v

Type 11 MCGN 4 Type I MCGN 6MCGN unclassified I Minimalchange IEnd stage renal failure I Membranous 5No renal lesion ITotal 7 12

frequency from that expected in normal age matchedpopulation. Similarly the fluorescein angiogramsshowed only a few hyperfluorescent spots corres-

ponding to scattered drusen.Of the seven patients with PLD (Table 4) five were

found to have a very striking abnormality in thefundi (Figs. 3,4,5). There was a regular, bilaterallysymmetrical distribution of discrete yellow spots,similar to drusen, more densely present posteriorlybut spreading up to and beyond the equator. Thelesions were not elevated, but were associated withsome 'irregularity' of pigmentation. In the same fivepatients fluorescein angiography showed grossabnormalities correlating with the drusen-likeappearance, and similar to that seen in the previouscase report,' with hyperfluorescence correspondingto the yellow lesions but with no leakage of fluores-cein. There was some variation from case to case inthe dimensions and distribution of the deposits, butthere was symmetry within each case. The visualacuity was unaffected. Four of these five cases hadbiopsy proved type II MCGN, and the fifth was likelyto be in this category on the basis of PLD andnephrotic syndrome, though no biopsy was ever

taken.Two patients with PLD had normal ophthalmo-

scopic and angiographic appearances. One hadunclassified MCGN, and the other had no evidenceof glomerular disease.

Fig. 2 Fundus photograph of case ]8 showing scattereddrusen at the posterior pole.

Discussion

We have described for the first time, to our know-ledge, in this and in our recent publication' an

abnormal deposit in the eye at the level of Bruch'smembrane and choriocapillaries in type II mesangio-capillary glomerulonephritis. Our findings in thiscommunication support the hypothesis that thechoriocapillaris - Bruch's membrane - retinalpigment epithelial complex may respond to disease ina similar way to the glomerulus.The previously reported fundus changes seen in

glomerular disease can be broadly divided into thoseassociated with hypertension, those associated withvasculitis causing glomerulonephritis, those resultingfrom treatment of the renal lesion, and those

Table 4 Oplithalmicfindings in cases wit/h PLD

Casa Visual acuity Fuiduls eratnitiatiOti Fluorescein angiography

R L

1 6/6 6/9 Massive drusen-like deposits and mottled Extensive hyperfluorescence in Bruch's membranepigmentation

2 6/6 6/5 Drusen-like deposits and mottled pigmentation Fess corresponding hyperfluorescent spots oserdrusen

3 6/6 6/6 Massise drusen-like deposits and mottled Extensive hyperfluorescencepigmentation

4 6/9 6/9 Massise drusen-like deposits and mottled Extensive hyperfluorescencepigmentation

5 6/36 6/24 Massive drusen-like deposits and mottled Extensive hyperfluorescencepigmentation

6 6/6 6/6 Normal Normal7 6/5 6/5 Massive drusen-like deposits and mottled Extensive hyperfluorescence in Bruch's membrane

pigmentation

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Fundits changes in mesangiocapillart glomeruilonephritis type /1

Pe-i. .As

Fi. 3(i

Fig. 3 A: Fundus photograph and B. C fluoresceinangiogram ofcase 4 showing large posterior pole depositswith a pigmented halo temporal to the macula, associatedwith intensefocal hyperfluorescence which extends towardsthe equator.

considered to be specifically related to the renallesion. In systemic hypertension the fundus abnorm-alities are well recognised, and they are described inrenal patients. In accelerated hypertension infarcts ofthe retinal pigment epithelium, corresponding tofailure of lobules of choriocapillaris to be perfused,termed Elschnig's spots, are described," but they

differ from the lesions we report in that they are muchmore widespread and are not associated with thefocal pigment clumping seen in Elschnig's spots. Inaddition there is no history of visual disturbancein any of our patients, whereas if there weresuch widespread infarction of the retinal pigmentepithelium visual symptoms would be expected.A series of patients with glomerulonephritis with

and without hypertension have been studied ophthal-moscopically. None of these showed any fluoresceinangiographic abnormality, though the type ofglomerulonephritis was not identified.

Vasculitis, such as is seen in systemic lupuserythematosus, may involve the renal circulation aswell as the retinal and choroidal circulation, givingrise to cotton-wool spots, hemorrhages, swelling ofthe optic nerve head, and vascular occlusion."' Inthe cases we have studied no features of vasculitiswere present.

Ocular complications of chronic renal diseaseinvolve exudative retinal detachment' and crystals ofcystine in the cornea and retina," and the complica-tions of treatment include cataract, raised intraocularpressure, opportunistic retinitis,' and retinal micro-aneurysms. '"A numer of familial disorders are described

which affect the eye and kidney. Those whichinvolve the retina and choroid include Alstrom'ssyndrome,'' which comprises pigmentary retino-pathy, obesity, diabetes mellitus, and nerve deafness,often associated with renal insufficiency; Alport'ssyndrome,'' which is characterized by lenticonus,spherophakia, sensorineural deafness, and ahereditary nephropathy and sometimes pigmentary

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J Dmvall- Young, C D Short, M F Raines, R Gokal, and W Law/er

lic. 4A

Fig. 4 A: Fundus photograph and B.fluiorescein angiograin of case 10 showtling scattered drusen-like deposits itith intensehVperfluorescence.

retinopathy with or without subretinal and Bruch'smembrane deposits; and adult polycystic kidneydisease."4 A miscellaneous group of hereditary renallesions associated with other fundus abnormalities,usually manifest as pigmentary retinopathies, aredescribed. 9' The only previous publicationscomparing pathology of the kidney and eye refer to

patients with diabetes mellitus: microaneurysms havebeen described in the glomerulus"' and lesionsresembling Kimmelsteil-Wilson nodules weredescribed in the choroid."'

Bruch's membrane and the glomerular membraneare structurally homologous in that both are. select-ively and directionally permeable,' with a positive

;io.5A Fig. 51lFig. 5 A: Fundus photograph and B,fluorescein angiogram ofcase 19 showing extensive drusen-like deposits withhyperfluorescence.

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Funds changes in mesangiocapillary glomerldonephritis type II

charge and a high heparan sulphate content. '"' Thetwo membranes differ in that the collagenous zonesof Bruch's membrane make it much thicker than theglomerular basement membrane. Pathologicalchanges in the renal glomerular basement membranewith similarities to those seen in Bruch's membraneare identifiable. In aging, the glomerular basementmembrane is focally thickened, with the appearanceof vesicles in the membranes similar to the agingchanges of Bruch's membrane.l In aminoglycosidenephrosis, deposits with an ultrastructural similarityto drusen are present on the epithelial side of theglomerular basement membrane.3" Aminoglycosidetoxicity has been used as an experimental means ofcreating drusen in the eye." Breaks in the glomerularbasement membrane, reminiscent of angioid streaksin Bruch's membrane, have also been described.4'The nature of deposits in different types of

glomerulonephritis differs histologically andpresumably also pathogenetically. We suggest that,whatever the pathogenesis in MCGN type II, asimilar setting pertains in Bruch's membrane,whereas in the other forms of glomerulonephritis thismay not be the case. Recently an early case of MCGNII has been studied histopathologically.4" It isinteresting that the early lesion prior to the appear-ance of the dense deposit is lamellation of the laminadensa of the glomerular basement membranes, veryreminiscent of the appearance seen in Alport'ssyndrome,4l which is undisputably associated with achorioretinal lesion.4' 1

Our findings suggest that, in patients with type IIMCGN and PLD, chorioretinal changes similarlymay parallel those found in the kidney. Although inall five patients with PLD and fundus changes theophthalmic findings were very similar, the durationof renal disease ranged from 7 months to 31 years,and sequential observation is necessary to determinewhether a lesion is static or variable with time. Thereis undoubtedly a structural and a pathologicalcomparison to be drawn between the eye and thekidney, and further investigation of patients withglomerular disease may well shed light on the patho-physiological responses of the complex of chorio-capillaris, Bruch's membrane, and retinal pigmentepithelial. Similarly, study of the ocular responsesmay contribute to the understanding of the patho-genesis of the renal lesion.

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Acce ptd for publication 4 Mai, 1989.

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