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Research Letters |

Extensive Drusen in Type I Membranoproliferative Glomerulonephritis FREE

Dennis P. Han, MD; Stephen Sievers, MD
Arch Ophthalmol. 2009;127(4):577-579. doi:10.1001/archophthalmol.2009.38.
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Published online

A case of extensive drusen formation associated with type I membranoproliferative glomerulonephritis (MPGN) is reported. Although similar findings have been noted with type II MPGN, to our knowledge this association has not been previously described in type I MPGN.

A 26-year-old woman was noted to have a fundus abnormality during a routine eye examination. Her medical history was significant for proteinuria and biopsy-confirmed type I MPGN developing in conjunction with meningococcal meningitis and meningococcemia 7 years previously. Serological analyses then showed low C3 and total complement levels. Renal biopsy with light and electron microscopy showed mesangial interposition, scattered subendothelial deposits, abundant immune complex deposits within the mesangium, and focal thickening of the glomerular basement membrane, consistent with type I MPGN. A repeat biopsy 5 years later showed immunohistopathologic staining of IgM and C3 in the mesangial capillary wall and glomerular basement membrane but no dense deposits indicative of type II MPGN. Her mother had senile cataracts. Two siblings were noted to have “normal eye exams” performed elsewhere.

On examination, visual acuity with spectacles was 20/30 OD and 20/20 OS. Near visual acuity was Jaeger 1+ OU. Anterior segment examination results were normal in both eyes. Ophthalmoscopy showed bilateral, multifocal, 200- to 300-μm, yellowish, elevated lesions at the choroid and subretinal pigment epithelial level, concentrating in the posterior pole but extending to the midperiphery (Figure 1). The peripheral lesions were most easily visualized overlying choroidal vessels. Optical coherence tomography showed multiple, optically lucent, focal elevations of the retinal pigment epithelium (Figure 2). Fluorescein angiography and indocyanine green angiography showed staining of lesions throughout the fundi, more numerous than those observed by ophthalmoscopy (Figure 3). Old fundus photographs (not shown) confirmed presence of the lesions 2 years previously, with gradual enlargement and increased confluency until examination 14 months after her initial visit to us. Visual acuity was unchanged.

Place holder to copy figure label and caption
Figure 1.

Red-free photographs show large drusenlike retinal pigment epithelial lesions in the central macula and temporal paramacular regions in the right (A) and left (B) eyes.

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Figure 2.

Optical coherence tomography of the right macula shows focal retinal pigment epithelial elevation corresponding to foveal retinal pigment epithelial lesions. Shadowing from a retinal arteriole is seen at the far right.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 3.

Fluorescein angiography shows staining of retinal pigment epithelial lesions in the macula of the right eye (A) and the superior midperiphery of the left eye (B). Indocyanine green angiography shows late hyperfluorescence of lesions in the temporal periphery of the right eye (C) and concentration of lesions near the superotemporal vortex veins of the left eye (D).

Graphic Jump Location

Extensive drusen formation has been described previously in association with type II MPGN.1,2 However, a MEDLINE search (1950 until the time of submission) revealed no citations of drusen formation in association with type I MPGN. In a study in which patients with various glomerulopathies were systematically examined for drusen, 5 patients with type II MPGN showed abnormal drusen formation, whereas 6 patients with type I MPGN showed no fundus abnormalities.1

The fundus lesions are described herein as drusen. However, they had a somewhat pale, homogeneous, yellow appearance similar to small retinal pigment epithelial detachments. The ophthalmoscopic distinction between large drusen and small serous retinal pigment epithelial detachments is said to be arbitrary.3 In type II MPGN, Duvall-Young et al1 described the lesions as being “similar” to drusen. They described significant variation in appearances of the lesions, some showing marked similarity to this case. Histopathologic studies also appear to justify the term drusen.4 In our case, the presence of hypocomplementemia and immunohistologic staining of C3 in the glomeruli suggests a role of complement activation in the drusen formation.

Whereas type II MPGN results from disinhibition of the alternative complement pathway, type I MPGN results from circulating immune complex deposition that can activate the classic complement pathway. Type I MPGN may be caused by a number of conditions that vary in duration and severity. Such variation may explain the absence of drusen in previously reported cases. Notably, drusen have also been observed in poststreptococcal glomerulonephritis, leading to the hypothesis that “distinct forms of glomerulonephritis with distinct etiologies may all result in the development of large drusen at a relatively early age.”4 The case reported herein further supports that hypothesis. Awareness of this association may be important clinically because of the documented occurrence of choroidal neovascularization with MPGN-related drusen.5

Correspondence: Dr Han, Department of Ophthalmology, Medical College of Wisconsin, 925 N 87th St, Milwaukee, WI 53226 (dhan@mcw.edu).

Author Contributions: Dr Han had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Financial Disclosure: None reported.

Funding/Support: This work was supported in part by Research to Prevent Blindness, Inc, New York, New York.

Duvall-Young  JShort  CRaines  MGokal  RLawler  W Fundus changes in mesangiocapillary glomerulonephritis type II: clinical and fluorescein angiographic findings. Br J Ophthalmol 1989;73 (11) 900- 906
PubMed Link to Article
Kim  DDMieler  WFWolf  MD Posterior segment changes in membranoproliferative glomerulonephritis. Am J Ophthalmol 1992;114 (5) 593- 599
PubMed
Green  WR Retina. Pathology of the macula. Spencer  WHOphthalmic Pathology: An Atlas and Textbook. 3rd ed. Philadelphia, PA WB Saunders1985;936- 961
Mullins  RRAptsiauri  NHageman  GS Structure and composition of drusen associated with glomerulonephritis: implications for the role of complement activation in drusen biogenesis. Eye 2001;15 (pt 3) 390- 395
PubMed Link to Article
Hassenstein  AGisbert  R Choroidal neovascularisation in type II membranoproliferative glomerulonephritis, photodynamic therapy as a treatment option: a case report [in German]. Klin Monatsbl Augenheilkd 2003;220 (7) 492- 495
PubMed Link to Article

Figures

Place holder to copy figure label and caption
Figure 1.

Red-free photographs show large drusenlike retinal pigment epithelial lesions in the central macula and temporal paramacular regions in the right (A) and left (B) eyes.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

Optical coherence tomography of the right macula shows focal retinal pigment epithelial elevation corresponding to foveal retinal pigment epithelial lesions. Shadowing from a retinal arteriole is seen at the far right.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 3.

Fluorescein angiography shows staining of retinal pigment epithelial lesions in the macula of the right eye (A) and the superior midperiphery of the left eye (B). Indocyanine green angiography shows late hyperfluorescence of lesions in the temporal periphery of the right eye (C) and concentration of lesions near the superotemporal vortex veins of the left eye (D).

Graphic Jump Location

Tables

References

Duvall-Young  JShort  CRaines  MGokal  RLawler  W Fundus changes in mesangiocapillary glomerulonephritis type II: clinical and fluorescein angiographic findings. Br J Ophthalmol 1989;73 (11) 900- 906
PubMed Link to Article
Kim  DDMieler  WFWolf  MD Posterior segment changes in membranoproliferative glomerulonephritis. Am J Ophthalmol 1992;114 (5) 593- 599
PubMed
Green  WR Retina. Pathology of the macula. Spencer  WHOphthalmic Pathology: An Atlas and Textbook. 3rd ed. Philadelphia, PA WB Saunders1985;936- 961
Mullins  RRAptsiauri  NHageman  GS Structure and composition of drusen associated with glomerulonephritis: implications for the role of complement activation in drusen biogenesis. Eye 2001;15 (pt 3) 390- 395
PubMed Link to Article
Hassenstein  AGisbert  R Choroidal neovascularisation in type II membranoproliferative glomerulonephritis, photodynamic therapy as a treatment option: a case report [in German]. Klin Monatsbl Augenheilkd 2003;220 (7) 492- 495
PubMed Link to Article

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