Retinal disease in the C3 glomerulopathies and the risk of impaired vision

ABSTRACT

Background: Dense deposit disease and atypical hemolytic uremic syndrome are often caused by Complement Factor H (CFH) mutations. This study describes the retinal abnormalities in dense deposit disease and, for the first time, atypical haemolytic uremic syndrome. It also reviews our understanding of drusen pathogenesis and their relevance for glomerular disease. Methods: Six individuals with dense deposit disease and one with atypical haemolytic uremic syndrome were studied from 2 to 40 years after presentation. Five had renal transplants. All four who had genetic testing had CFH mutations. Individuals underwent ophthalmological review and retinal photography, and in some cases, optical coherence tomography, and further tests of retinal function. Results: All subjects with dense deposit disease had impaired night vision and retinal drusen or whitish-yellow deposits. Retinal atrophy, pigmentation, and hemorrhage were common. In late disease, peripheral vision was restricted, central vision was distorted, and there were scotoma from sub-retinal choroidal neovascular membranes and atypical serous retinopathy. Drusen were present but less prominent in the young person with atypical uremic syndrome due to a heterozygous CFH mutation. Conclusions: Drusen are common in forms of C3 glomerulopathy caused by compound heterozygous or heterozygous CFH mutations. They are useful diagnostically but also impair vision. Drusen have an identical composition to glomerular deposits. They are also identical to the drusen of age-related macular degeneration, and may respond to the same treatments. Individuals with a C3 glomerulopathy should be assessed ophthalmologically at diagnosis, and monitored regularly for vision-threatening complications.

KEYWORDS:

• C3 glomerulopathy
• complement alternative pathway
• complement factor H
• dense deposit disease
• drusen
• membranoproliferative glomerulonephritis type II

Acknowledgements

We would like to thank Gary Wyatt of Topcon (Australia) who helped us with the initial investigations. We would also like to thank the patients who took part in these studies. The retinal photographs were taken with the approval of the Austin and Northern Health IRBs, according to the Declaration of Helsinki, and all participants provided signed, informed consent.

Patient 1 was described previously in a manuscript published in American Journal of Kidney Diseases in 2003 but otherwise none of the results in this study have been published in whole or part except in abstract form.

Declaration of interest

Peter Hughes has received funding for clinical studies from a company that produces antiC5 antibodies but this has no relationship with the work described here. The other authors report no conflicts of interest. The authors alone are responsible for the writing and content of this article.