P HARRAKA1, H MACK1,2,3, D COLVILLE1, D BARIT1, D LANGSFORD1, T PIANTA1, J SAVIGE1
1The University Of Melbourne Department of Medicine, Northern Health, Epping 3076, Australia, 2The University of Melbourne Department of Surgery (Ophthalmology), Royal Victorian Eye and Ear Hospital, East Melbourne 3002, Australia, 3Department of Ophthalmology, Melbourne Health, Parkville 3050, Australia
Background: Drusen are white-yellow flecks visible on ophthalmoscopy, located between the retinal pigment epithelial cells and Bruch’s membrane, and associated with complement activation. Drusen are similar in composition to glomerular immune deposits and the underlying mechanisms may partly explain immune glomerulonephritis pathogenesis. Renal immune deposits in membranous and anti-glomerular basement membrane (GBM) glomerulonephritis result from antibodies to glomerular antigens (PLA2R, THSD7A and collagen IV a3 respectively) which are also expressed in the retina. In contrast, anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis is associated with complement activation but not glomerular immune deposits. This study examined clinical patients with these diseases for retinal drusen.
Method: This was a cross-sectional observational study of 16 individuals with antibody-mediated glomerulonephritis (n=16, membranous n=10, anti-GBM disease n=6) and 16 with pauci-immune vasculitis recruited from a general renal clinic of a tertiary-care metropolitan hospital. Retinal images were taken using a non-mydriatic retinal camera and assessed for drusen number (≥10 centrally), location and size by two trained graders, and atrophy and pigmentation by an ophthalmologist.
Results: There was no difference in gender (p=1.00), age (p=0.98), disease duration (p=0.36), immunosuppression (p=0.08) or transplantation (p=0.10) between groups. Central drusen counts ≥10 occurred in four (25%) participants with immune-complex glomerulonephritis and one (6%) with vasculitis (OR=5.00, 95% CI: 0.49 to 50.8, p=0.33). The individual with vasculitis and drusen also had IgA nephropathy. Few had medium or large drusen and none had atrophy or pigmentation.
Conclusions: Drusen are seen in a minority with immune-complex glomerulonephritis and less often in pauci-immune vasculitis. Whether drusen can be used as a non-invasive biomarker of disease progression warrants further attention. Treatments targeting drusen may be effective against renal immune deposits in glomerulonephritis.
Philip Harraka is a third year PhD student at The University of Melbourne, Department of Medicine. He is the symposium lead for the Australian Society of Medical Research (ASMR). His PhD investigated the “Genetics of IgA nephropathy” with focus on families with inherited renal disease. This PhD also investigated retinal drusen in glomerular disease to identify shared pathogenetic mechanisms. Treatments targeting macular degeneration may prove effective against IgA nephropathy and other immune complex glomerulonephritis