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Visual impairment caused by retinal abnormalities in mesangiocapillary (membranoproliferative) glomerulonephritis type II (“dense deposit disease”)
CASE REPORT
Visual Impairment Caused by Retinal Abnormalities in Mesangiocapillary (Membranoproliferative) Glomerulonephritis Type II (“Dense Deposit Disease”) Deb Colville, MB FRACO, Robyn Guymer, FRACO, PhD, Roger A. Sinclair, FRCPA, MD, and Judy Savige, FRACP, PhD ● Patients with mesangiocapillary glomerulonephritis (MCGN) type II usually present by early adulthood with hematuria, proteinuria, and renal impairment, and these features often are accompanied by a partial lipodystrophy and an autoantibody for the alternative complement pathway convertase (C3NeF). The diagnosis of MCGN type II depends on the demonstration of “dense deposits” in the glomerular basement membrane (GBM). Most patients also have multiple subretinal white spots or drusen that are histopathologically identical with the GBM deposits and evident ophthalmoscopically by the time renal failure develops. Initially visual acuity and visual fields are preserved, but fluorescein angiography and specialized tests of retinal function, such as dark adaptation, electroretinography, and electrooculography, may be abnormal and will worsen progressively. Over the next 20 years, vision often deteriorates because of retinal atrophy, and sometimes because of subretinal neovascular membranes, macular detachment, and central serous retinopathy. The authors describe a patient with MCGN type II who presented with renal failure and impaired vision at the age of 59. He already had widespread retinal atrophy, and subsequently a subretinal membrane developed. The drusen seen in MCGN type II, like the partial lipodystrophy, are a helpful clinical pointer to the diagnosis of this condition. All patients with MCGN type II should be warned of the risk of retinal complications and reviewed by an ophthalmologist at presentation and regularly after about 10 years to minimize the loss of visual acuity from complications of the retinopathy. Am J Kidney Dis 42:E3. © 2003 by the National Kidney Foundation, Inc. INDEX WORDS: Drusen; membranoproliferative glomerulonephritis (MPGN); mesangiocapillary glomerulonephritis (MCGN) type II; retinopathy; retinal atrophy.
M
ESANGIOCAPILLARY (MCGN) or membranoproliferative glomerulonephritis accounts for about 10% of all cases of glomerular disease,1 and MCGN type II causes fewer than 20% of these.2 Patients with MCGN type II usually present by early adulthood with hematuria, proteinuria, and renal impairment. Many have a lipodystrophy affecting the face and shoulders3-5 that is contemporaneous with the renal disease. Seventy percent have C3 nephritic factor (C3NeF), an autoantibody directed against C3bBb, the alternative pathway convertase3,6 that results in normal C4 levels but low C3 because of persistent activation of the alternative complement pathway. Renal cells and adipocytes both express complement components, and C3NeFinduced activation of the alternative pathway results in complement-mediated injury affecting the kidney and fatty tissues.7 Most patients with MCGN type II appear to have sporadic disease, but some have obvious X-linked, autosomal dominant or recessive inheritance.3,8-10 Clinical and histopathologic features are similar with all forms of inheritance, but the mutant genes have not yet been identified.
The diagnosis of MCGN type II depends on the ultrastructural demonstration of dense intramembranous deposits in the glomerular basement membrane (GBM). Most patients with MCGN type II also have a distinctive retinal appearance with multiple subretinal whitishyellow spots or drusen that are evident ophthalmoscopically by the time renal failure develops (Fig 1).11-13 The drusen are mainly central and clustered, 11,12,14-22 but larger soft drusen also are seen. Drusen increase in number over the years From the Centre for Eye Research, University Department of Ophthalmology, Royal Victorian Eye and Ear Hospital, East Melbourne and the Departments of Anatomical Pathology and Medicine, Austin; and Repatriation Medical Centre, Heidelberg, Victoria, Australia. Received August 21, 2002; accepted in revised form March 20, 2003. Supported by the National Health and Medical Research Council of Australia. Address reprint requests to A/Prof Judy Savige, FRACP, PhD, University Department of Medicine, Austin and Repatriation Medical Centre, Heidelberg VIC 3084, Australia. E-mail: [email protected] © 2003 by the National Kidney Foundation, Inc. 0272-6386/03/4202-0021$30.00/0 doi:10.1016/S0272-6386(03)00665-6
American Journal of Kidney Diseases, Vol 42, No 2 (August), 2003: E3
1
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COLVILLE ET AL
Fig 1. Typical fundus view in MCGN type II shows multiple, small, well-defined macular drusen.
At the time of presentation, the patient had no visual symptoms apart from poor night vision. However, at a formal ophhthalmologic assessment 2 years after presentation, his vision was 6/12 in the right eye and 6/9 in the left, with a large central scotoma in each eye and restricted peripheral fields. Over the next 15 years, the patient was reviewed by several ophthalmologists, but the basis of his retinal abnormality was still not recognized. He underwent a number of specialized investigations, including an Ishihara test early in the disease, the results of which were normal, indicating intact color vision; a “dark adaptation” test that was uniphasic, consistent with severe rod dysfunction; electroretinography (ERG) that detected delayed rod and delayed combined rod and cone responses; and electrooculography (EOG) that showed a reduced light peak/dark trough (or Arden ratio) possibly reflecting an obstruction to the passage of metabolites from the choriocapillaris. A retinal fluorescein angiogram 8 years after presentation showed widespread chorioretinal degeneration and atrophy. A second angiogram detected subfoveal neovascularisation, which
to produce multiple bilaterally symmetrical discrete spots. The drusen are histopathologically identical with the GBM deposits11 and probably result from the leakage of abnormal material through the damaged vessel walls and constitute a “dense deposit retinopathy.” The retina and glomerulus both comprise fenestrated capillaries, and the choriocapillaries, Bruch’s membrane, and retinal pigment epithelium resemble the glomerular tufts, GBM, and glomerular epithelium, respectively. However, the retinopathy and its association with MCGN type II are often unrecognized. We describe here a patient who presented with renal failure in late-middle age and whose retinal abnormality was first identified many years later at a time when complications had resulted in severe visual loss. PATIENT The patient was a 78-year-old Italian man who presented at the age of 59 with an acute myocardial infarct and was found to have a serum creatinine level of 8.5 mg/dL (750 mol/L). On examination, no specific diagnostic features were noted except for occasional drusen, a widespread bilateral chorioretinal atrophy, and macular pigmentation on ophthalmoscopy (Fig 2A). The significance of the retinal lesions was not realized. A renal biopsy was performed and showed MCGN type II (Fig 2B), and the patient was noted in retrospect to have the long thin face consistent with a partial lipodystrophy. Complement levels were not measured. His renal function subsequently improved, but he began dialysis 6 months later and underwent transplantation after a further 3 years.
Fig 2. (A) Fundus view in the patient at the age of 66 years, 7 years after presentation with renal failure caused by MCGN type II, shows retinal atrophy with prominent pigment clumping secondary to a neovascular membrane. (B) Electron microscopic appearance of the renal biopsy from the patient shows homogeneous electron dense ribbonlike material within the glomerular basement membrane and mesangium consistent with the diagnosis of MCGN type II.
RETINAL ABNORMALITIES IN MCGN TYPE II
was not treated. A third angiogram showed large patches of hyperfluorescence with sharply demarcated borders at the left fovea consistent with a subfoveal patch of fibrosis or net, which was considered untreatable. By this time, the patient was only able to recognize shapes and light and dark. The diagnosis of retinal complications resulting from MCGN type II was made eventually by an ophthalmologist with an interest in the ocular manifestations of renal disease 2 years before the patient died of acute myeloid leukemia.
DISCUSSION
Most patients with MCGN type II have renal failure by their third decade, but the patient described here was 59 years old at presentation. He had few of the retinal drusen seen in younger patients but had widespread retinal atrophy and pigmentation. He survived for a further 19 years, which was sufficient time for major retinal complications to ensue. We are likely to see more patients with MCGN type II who survive for many years after renal transplantation and who experience visual impairment from retinal disease. Patients with MCGN type II usually have normal visual acuity and visual fields at presentation. Fifteen years later, night vision is abnormal, and visual acuity and visual fields are often impaired. These abnormalities correspond to the presence of retinal atrophy and retinal pigment epithelium clumping on fundoscopy, and the patient described here presented at this stage. Other ocular complications include subretinal neovascularisation, which eventually occurs in one third of patients,18 and retinal detachment and central serous retinopathy,19 which are less frequent. Subretinal neovascular membranes are present mainly in the macular region, may be bilateral,18 and result in visual loss caused by bleeding, exudation, and subsequent scar formation. Patients notice a loss of visual acuity or visual fields with these complications. A number of specialized ophthalmologic investigations are abnormal in the retinopathy of MCGN type II. “Dark adaptation” is abnormal in patients with impaired night vision and in those with the more severe fundus abnormalities. The “rod-cone break” is delayed or absent, and the rod and cone “thresholds” are at the upper limits of normal or elevated. ERG results are usually normal early21 but become abnormal, especially when patients have difficulty seeing in the dark.16,20 The ERG rod and combined rod and
3
cone responses may be attenuated or delayed. Cone responses are more likely to be normal.20 EOG results may be abnormal even with clinically normal vision. Deposits in Bruch’s membrane and the choriocapillaris disturb retinal pigment epithelial function by obstructing the diffusion of metabolites from the choriocapillaris and causing a reduction in the light peak/dark trough (Arden ratio). The EOG abnormalities are more marked in individuals with a marked retinopathy or subretinal neovascularisation.18 Fluorescein angiography usually shows abnormalities even when fundoscopy is normal.12 Drusen may be evident, but there is no fluorescein leakage. Later there is variegated fluorescence from areas of mottled retinal pigment atrophy and clumping.17 Indocyanine green angiography can indicate choroidal new vessel formation despite pigment or blood obscuring these in the clinical examination and on fluorescein angiogram. Vitreous fluorophotometry has shown that the deposits cause the blood-retinal barrier at the tight junctions of the retinal pigment epithelial and endothelial cells to be leakier than with other types of drusen.22 What else could cause this retinal abnormality? The drusen in MCGN type II resemble those seen in age-related macular degeneration, which is also associated with retinal atrophy, pigmentation, and neovascular membranes, but patients with macular degeneration are usually older, and abnormalities are typically perimacular. The drusen in another inherited renal disease, Alport syndrome, are small and perimacular, vision is normal, retinal complications are rare, and deafness and lenticonus are often present. Retinitis pigmentosa is associated with renal failure in medullary cystic disease and Laurence-MoonBiedl syndrome, but the optic disc is pale, and the vessels are narrowed. The retinopathy in accelerated hypertension comprises pigment epithelial infarcts and pigment clumping, and in systemic lupus erythematosus a vasculitis affecting the retinal and choroidal circulations produces “cottonwool” spots, hemorrhages, and optic disc swelling. The retinal drusen seen in MCGN type II, like the partial lipodystrophy, are helpful clinical pointers to the diagnosis of this condition. All patients with MCGN type II should be reviewed by an ophthalmologist at presentation and annu-
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COLVILLE ET AL
ally after about 10 years to minimize the risk of visual loss from complications of the retinopathy. Patients should be warned to return for review immediately if their vision “changes” because of the risk of a neovascular membrane. Fluorescein or indocyanine green angiography shows these membranes, and early laser treatment will help preserve vision.18 REFERENCES 1. Simon P, Ramee MP, Autuly V, et al: Epidemiology of primary glomerular diseases in a French region. Variations according to period and age. Kidney Int 46:1192-1198, 1994 2. Habib R, Gubler MC, Loirat C, Maiz HB, Levy M: Dense deposit disease: A variant of membranoproliferative glomerulonephritis. Kidney Int 7:204-215, 1975 3. Power DA, Ng YC, Simpson JG: Familial incidence of C3 nephritic factor, partial lipodystrophy and membranoproliferative glomeruloneprhitis. Q J Med 75:387-398, 1990 4. Eisinger AJ, Shortland JR, Moorhead PJ: Renal disease in partial lipodystrophy. QJM 41:343-354, 1972 5. Spitzer RE, Vallota EH, Forristal J, et al: Serum C’3 lytic system in patients with glomerulonephritis. Science 164:436-437, 1969 6. Scott DM, Amos N, Sissons JG, Lachmann PJ, Peters DK: The immunoglobulin nature of nephritic factor (NeF). Clin Exp Immunol 32:12-24, 1978 7. Mathieson PW, Wurzner R, Oliveira DBG, Lachmann PJ, Peters DK: Complement-mediated adipocyte lysis by nephritis factor sera. J Exp Med 177:1827-1831, 1993 8. Berry PL, McEnery PT, McAdams AJ, West CD: Membranoproliferative glomerulonephritis in 2 sibships. Clin Nephrol 16:101-106, 1981 9. Stutchfield PR, White RHR, Cameron AH, Thompson RA, Mackintosh P, Wells L: X-linked mesangiocapillary glomerulonephritis. Clin Nephrol 26:150-156, 1986 10. Bakkaloglu A, Soylemezoglu O, Tinaztepe K, Saatci U, Soylemezglu F: Familial membranoproliferative glomerulonephritis. Nephrol Dial Tranpslant 10:21-24, 1995 11. Duvall-Young J, Macdonald MK, McKechnie NM: Fundus changes in (type II) mesangiocapillary glomerulonephritis simulating drusen: A histopathological report. Br J Ophthalmol 73:297-302, 1989
12. Leys A, Vanrenterghem Y, Van Damme B, Snyers B, Pirson Y, Leys M: Fundus changes in membranoproliferative glomerulonephritis type II. A fluorescein angiographic study of 23 patients. Arch Clin Exp Ophthalmol 229:406410, 1991 13. Davis TM, Holdright DR, Schulenberg WE, Turner RC, Joplin GF: Retinal pigment epithelial change and partial lipodystrophy. Postgrad Med J 64:871-874, 1988 14. Duvall-Young J, Short CD, Raines MF, Gokal R, Lawler W: Fundus changes in mesangiocapillary glomerulonephritis type II: Clinical and fluorescein angiographic findings. Br J Ophthalmol 73:900-906, 1989 15. Leys A, Proesmans W, van Damme-Lombaerts R, Van Damme B: Specific eye fundus lesions in type II membranoproliferative glomerulonephritis. Paediatr Nephrol 5:189-192, 1991 16. Michielsen B, Leys A, Van Damme B, Missotten L: Fundus changes in chronic membranoproliferative glomerulonephritis type II. Documenta Ophthalmologica 76:219229, 1991 17. Kim DD, Mieler WF, Wolf MD: Posterior segment changes in membranoproliferative glomerulonephritis. Am J Ophthalmol 114:593-599, 1992 18. Leys A, Michielsen B, Leys M, Vanrenterghem Y, Missotten L, Van Damme B: Subretinal neovascular membranes associated with chronic membranoproliferative glomerulonephritis type II. Arch Clin Exp Ophthalmol 228:499504, 1990 19. Ulbig MRW, Riordan-Eva P, Holz FG, Rees HC, Hamilton PAM: Membranoproliferative glomerulonephritis type II associated with central serous retinopathy. Am J Ophthalmol 116:410-413, 1993 20. Kim RY, Faktorovich EG, Kuo CY, Olson JL: Retinal function abnormalities in membranoproliferative glomerulonephritis type II. Am J Ophthalmol 123:619-628, 1997 21. O’Brien C, Duvall-Young J, Brown M, Short C, Bone M: Electrophysiology of type II mesangiocapillary glomerulonephritis with associated fundus abnormalities. Br J Ophthalmol 77:778-780, 1993 22. Raines MF, Duvall-Young J, Short CD: Fundus changes in mesangiocapillary glomerulonephritis type II: Vitreous fluorophotometry. Br J Ophthalmol 73:907-910, 1989
Visual Impairment Caused by Retinal Abnormalities in Mesangiocapillary (Membranoproliferative) Glomerulonephritis Type II (“Dense Deposit Disease”) Deb Colville, MB FRACO, Robyn Guymer, FRACO, PhD, Roger A. Sinclair, FRCPA, MD, and Judy Savige, FRACP, PhD ● Patients with mesangiocapillary glomerulonephritis (MCGN) type II usually present by early adulthood with hematuria, proteinuria, and renal impairment, and these features often are accompanied by a partial lipodystrophy and an autoantibody for the alternative complement pathway convertase (C3NeF). The diagnosis of MCGN type II depends on the demonstration of “dense deposits” in the glomerular basement membrane (GBM). Most patients also have multiple subretinal white spots or drusen that are histopathologically identical with the GBM deposits and evident ophthalmoscopically by the time renal failure develops. Initially visual acuity and visual fields are preserved, but fluorescein angiography and specialized tests of retinal function, such as dark adaptation, electroretinography, and electrooculography, may be abnormal and will worsen progressively. Over the next 20 years, vision often deteriorates because of retinal atrophy, and sometimes because of subretinal neovascular membranes, macular detachment, and central serous retinopathy. The authors describe a patient with MCGN type II who presented with renal failure and impaired vision at the age of 59. He already had widespread retinal atrophy, and subsequently a subretinal membrane developed. The drusen seen in MCGN type II, like the partial lipodystrophy, are a helpful clinical pointer to the diagnosis of this condition. All patients with MCGN type II should be warned of the risk of retinal complications and reviewed by an ophthalmologist at presentation and regularly after about 10 years to minimize the loss of visual acuity from complications of the retinopathy. Am J Kidney Dis 42:E3. © 2003 by the National Kidney Foundation, Inc. INDEX WORDS: Drusen; membranoproliferative glomerulonephritis (MPGN); mesangiocapillary glomerulonephritis (MCGN) type II; retinopathy; retinal atrophy.
M
ESANGIOCAPILLARY (MCGN) or membranoproliferative glomerulonephritis accounts for about 10% of all cases of glomerular disease,1 and MCGN type II causes fewer than 20% of these.2 Patients with MCGN type II usually present by early adulthood with hematuria, proteinuria, and renal impairment. Many have a lipodystrophy affecting the face and shoulders3-5 that is contemporaneous with the renal disease. Seventy percent have C3 nephritic factor (C3NeF), an autoantibody directed against C3bBb, the alternative pathway convertase3,6 that results in normal C4 levels but low C3 because of persistent activation of the alternative complement pathway. Renal cells and adipocytes both express complement components, and C3NeFinduced activation of the alternative pathway results in complement-mediated injury affecting the kidney and fatty tissues.7 Most patients with MCGN type II appear to have sporadic disease, but some have obvious X-linked, autosomal dominant or recessive inheritance.3,8-10 Clinical and histopathologic features are similar with all forms of inheritance, but the mutant genes have not yet been identified.
The diagnosis of MCGN type II depends on the ultrastructural demonstration of dense intramembranous deposits in the glomerular basement membrane (GBM). Most patients with MCGN type II also have a distinctive retinal appearance with multiple subretinal whitishyellow spots or drusen that are evident ophthalmoscopically by the time renal failure develops (Fig 1).11-13 The drusen are mainly central and clustered, 11,12,14-22 but larger soft drusen also are seen. Drusen increase in number over the years From the Centre for Eye Research, University Department of Ophthalmology, Royal Victorian Eye and Ear Hospital, East Melbourne and the Departments of Anatomical Pathology and Medicine, Austin; and Repatriation Medical Centre, Heidelberg, Victoria, Australia. Received August 21, 2002; accepted in revised form March 20, 2003. Supported by the National Health and Medical Research Council of Australia. Address reprint requests to A/Prof Judy Savige, FRACP, PhD, University Department of Medicine, Austin and Repatriation Medical Centre, Heidelberg VIC 3084, Australia. E-mail: [email protected] © 2003 by the National Kidney Foundation, Inc. 0272-6386/03/4202-0021$30.00/0 doi:10.1016/S0272-6386(03)00665-6
American Journal of Kidney Diseases, Vol 42, No 2 (August), 2003: E3
1
2
COLVILLE ET AL
Fig 1. Typical fundus view in MCGN type II shows multiple, small, well-defined macular drusen.
At the time of presentation, the patient had no visual symptoms apart from poor night vision. However, at a formal ophhthalmologic assessment 2 years after presentation, his vision was 6/12 in the right eye and 6/9 in the left, with a large central scotoma in each eye and restricted peripheral fields. Over the next 15 years, the patient was reviewed by several ophthalmologists, but the basis of his retinal abnormality was still not recognized. He underwent a number of specialized investigations, including an Ishihara test early in the disease, the results of which were normal, indicating intact color vision; a “dark adaptation” test that was uniphasic, consistent with severe rod dysfunction; electroretinography (ERG) that detected delayed rod and delayed combined rod and cone responses; and electrooculography (EOG) that showed a reduced light peak/dark trough (or Arden ratio) possibly reflecting an obstruction to the passage of metabolites from the choriocapillaris. A retinal fluorescein angiogram 8 years after presentation showed widespread chorioretinal degeneration and atrophy. A second angiogram detected subfoveal neovascularisation, which
to produce multiple bilaterally symmetrical discrete spots. The drusen are histopathologically identical with the GBM deposits11 and probably result from the leakage of abnormal material through the damaged vessel walls and constitute a “dense deposit retinopathy.” The retina and glomerulus both comprise fenestrated capillaries, and the choriocapillaries, Bruch’s membrane, and retinal pigment epithelium resemble the glomerular tufts, GBM, and glomerular epithelium, respectively. However, the retinopathy and its association with MCGN type II are often unrecognized. We describe here a patient who presented with renal failure in late-middle age and whose retinal abnormality was first identified many years later at a time when complications had resulted in severe visual loss. PATIENT The patient was a 78-year-old Italian man who presented at the age of 59 with an acute myocardial infarct and was found to have a serum creatinine level of 8.5 mg/dL (750 mol/L). On examination, no specific diagnostic features were noted except for occasional drusen, a widespread bilateral chorioretinal atrophy, and macular pigmentation on ophthalmoscopy (Fig 2A). The significance of the retinal lesions was not realized. A renal biopsy was performed and showed MCGN type II (Fig 2B), and the patient was noted in retrospect to have the long thin face consistent with a partial lipodystrophy. Complement levels were not measured. His renal function subsequently improved, but he began dialysis 6 months later and underwent transplantation after a further 3 years.
Fig 2. (A) Fundus view in the patient at the age of 66 years, 7 years after presentation with renal failure caused by MCGN type II, shows retinal atrophy with prominent pigment clumping secondary to a neovascular membrane. (B) Electron microscopic appearance of the renal biopsy from the patient shows homogeneous electron dense ribbonlike material within the glomerular basement membrane and mesangium consistent with the diagnosis of MCGN type II.
RETINAL ABNORMALITIES IN MCGN TYPE II
was not treated. A third angiogram showed large patches of hyperfluorescence with sharply demarcated borders at the left fovea consistent with a subfoveal patch of fibrosis or net, which was considered untreatable. By this time, the patient was only able to recognize shapes and light and dark. The diagnosis of retinal complications resulting from MCGN type II was made eventually by an ophthalmologist with an interest in the ocular manifestations of renal disease 2 years before the patient died of acute myeloid leukemia.
DISCUSSION
Most patients with MCGN type II have renal failure by their third decade, but the patient described here was 59 years old at presentation. He had few of the retinal drusen seen in younger patients but had widespread retinal atrophy and pigmentation. He survived for a further 19 years, which was sufficient time for major retinal complications to ensue. We are likely to see more patients with MCGN type II who survive for many years after renal transplantation and who experience visual impairment from retinal disease. Patients with MCGN type II usually have normal visual acuity and visual fields at presentation. Fifteen years later, night vision is abnormal, and visual acuity and visual fields are often impaired. These abnormalities correspond to the presence of retinal atrophy and retinal pigment epithelium clumping on fundoscopy, and the patient described here presented at this stage. Other ocular complications include subretinal neovascularisation, which eventually occurs in one third of patients,18 and retinal detachment and central serous retinopathy,19 which are less frequent. Subretinal neovascular membranes are present mainly in the macular region, may be bilateral,18 and result in visual loss caused by bleeding, exudation, and subsequent scar formation. Patients notice a loss of visual acuity or visual fields with these complications. A number of specialized ophthalmologic investigations are abnormal in the retinopathy of MCGN type II. “Dark adaptation” is abnormal in patients with impaired night vision and in those with the more severe fundus abnormalities. The “rod-cone break” is delayed or absent, and the rod and cone “thresholds” are at the upper limits of normal or elevated. ERG results are usually normal early21 but become abnormal, especially when patients have difficulty seeing in the dark.16,20 The ERG rod and combined rod and
3
cone responses may be attenuated or delayed. Cone responses are more likely to be normal.20 EOG results may be abnormal even with clinically normal vision. Deposits in Bruch’s membrane and the choriocapillaris disturb retinal pigment epithelial function by obstructing the diffusion of metabolites from the choriocapillaris and causing a reduction in the light peak/dark trough (Arden ratio). The EOG abnormalities are more marked in individuals with a marked retinopathy or subretinal neovascularisation.18 Fluorescein angiography usually shows abnormalities even when fundoscopy is normal.12 Drusen may be evident, but there is no fluorescein leakage. Later there is variegated fluorescence from areas of mottled retinal pigment atrophy and clumping.17 Indocyanine green angiography can indicate choroidal new vessel formation despite pigment or blood obscuring these in the clinical examination and on fluorescein angiogram. Vitreous fluorophotometry has shown that the deposits cause the blood-retinal barrier at the tight junctions of the retinal pigment epithelial and endothelial cells to be leakier than with other types of drusen.22 What else could cause this retinal abnormality? The drusen in MCGN type II resemble those seen in age-related macular degeneration, which is also associated with retinal atrophy, pigmentation, and neovascular membranes, but patients with macular degeneration are usually older, and abnormalities are typically perimacular. The drusen in another inherited renal disease, Alport syndrome, are small and perimacular, vision is normal, retinal complications are rare, and deafness and lenticonus are often present. Retinitis pigmentosa is associated with renal failure in medullary cystic disease and Laurence-MoonBiedl syndrome, but the optic disc is pale, and the vessels are narrowed. The retinopathy in accelerated hypertension comprises pigment epithelial infarcts and pigment clumping, and in systemic lupus erythematosus a vasculitis affecting the retinal and choroidal circulations produces “cottonwool” spots, hemorrhages, and optic disc swelling. The retinal drusen seen in MCGN type II, like the partial lipodystrophy, are helpful clinical pointers to the diagnosis of this condition. All patients with MCGN type II should be reviewed by an ophthalmologist at presentation and annu-
4
COLVILLE ET AL
ally after about 10 years to minimize the risk of visual loss from complications of the retinopathy. Patients should be warned to return for review immediately if their vision “changes” because of the risk of a neovascular membrane. Fluorescein or indocyanine green angiography shows these membranes, and early laser treatment will help preserve vision.18 REFERENCES 1. Simon P, Ramee MP, Autuly V, et al: Epidemiology of primary glomerular diseases in a French region. Variations according to period and age. Kidney Int 46:1192-1198, 1994 2. Habib R, Gubler MC, Loirat C, Maiz HB, Levy M: Dense deposit disease: A variant of membranoproliferative glomerulonephritis. Kidney Int 7:204-215, 1975 3. Power DA, Ng YC, Simpson JG: Familial incidence of C3 nephritic factor, partial lipodystrophy and membranoproliferative glomeruloneprhitis. Q J Med 75:387-398, 1990 4. Eisinger AJ, Shortland JR, Moorhead PJ: Renal disease in partial lipodystrophy. QJM 41:343-354, 1972 5. Spitzer RE, Vallota EH, Forristal J, et al: Serum C’3 lytic system in patients with glomerulonephritis. Science 164:436-437, 1969 6. Scott DM, Amos N, Sissons JG, Lachmann PJ, Peters DK: The immunoglobulin nature of nephritic factor (NeF). Clin Exp Immunol 32:12-24, 1978 7. Mathieson PW, Wurzner R, Oliveira DBG, Lachmann PJ, Peters DK: Complement-mediated adipocyte lysis by nephritis factor sera. J Exp Med 177:1827-1831, 1993 8. Berry PL, McEnery PT, McAdams AJ, West CD: Membranoproliferative glomerulonephritis in 2 sibships. Clin Nephrol 16:101-106, 1981 9. Stutchfield PR, White RHR, Cameron AH, Thompson RA, Mackintosh P, Wells L: X-linked mesangiocapillary glomerulonephritis. Clin Nephrol 26:150-156, 1986 10. Bakkaloglu A, Soylemezoglu O, Tinaztepe K, Saatci U, Soylemezglu F: Familial membranoproliferative glomerulonephritis. Nephrol Dial Tranpslant 10:21-24, 1995 11. Duvall-Young J, Macdonald MK, McKechnie NM: Fundus changes in (type II) mesangiocapillary glomerulonephritis simulating drusen: A histopathological report. Br J Ophthalmol 73:297-302, 1989
12. Leys A, Vanrenterghem Y, Van Damme B, Snyers B, Pirson Y, Leys M: Fundus changes in membranoproliferative glomerulonephritis type II. A fluorescein angiographic study of 23 patients. Arch Clin Exp Ophthalmol 229:406410, 1991 13. Davis TM, Holdright DR, Schulenberg WE, Turner RC, Joplin GF: Retinal pigment epithelial change and partial lipodystrophy. Postgrad Med J 64:871-874, 1988 14. Duvall-Young J, Short CD, Raines MF, Gokal R, Lawler W: Fundus changes in mesangiocapillary glomerulonephritis type II: Clinical and fluorescein angiographic findings. Br J Ophthalmol 73:900-906, 1989 15. Leys A, Proesmans W, van Damme-Lombaerts R, Van Damme B: Specific eye fundus lesions in type II membranoproliferative glomerulonephritis. Paediatr Nephrol 5:189-192, 1991 16. Michielsen B, Leys A, Van Damme B, Missotten L: Fundus changes in chronic membranoproliferative glomerulonephritis type II. Documenta Ophthalmologica 76:219229, 1991 17. Kim DD, Mieler WF, Wolf MD: Posterior segment changes in membranoproliferative glomerulonephritis. Am J Ophthalmol 114:593-599, 1992 18. Leys A, Michielsen B, Leys M, Vanrenterghem Y, Missotten L, Van Damme B: Subretinal neovascular membranes associated with chronic membranoproliferative glomerulonephritis type II. Arch Clin Exp Ophthalmol 228:499504, 1990 19. Ulbig MRW, Riordan-Eva P, Holz FG, Rees HC, Hamilton PAM: Membranoproliferative glomerulonephritis type II associated with central serous retinopathy. Am J Ophthalmol 116:410-413, 1993 20. Kim RY, Faktorovich EG, Kuo CY, Olson JL: Retinal function abnormalities in membranoproliferative glomerulonephritis type II. Am J Ophthalmol 123:619-628, 1997 21. O’Brien C, Duvall-Young J, Brown M, Short C, Bone M: Electrophysiology of type II mesangiocapillary glomerulonephritis with associated fundus abnormalities. Br J Ophthalmol 77:778-780, 1993 22. Raines MF, Duvall-Young J, Short CD: Fundus changes in mesangiocapillary glomerulonephritis type II: Vitreous fluorophotometry. Br J Ophthalmol 73:907-910, 1989