Retinal findings in glomerulonephritis

ABSTRACT

The complement system is part of the innate immune system activated by three distinct pathways: classical, lectin and alternative. It is also involved in retinal development and homoeostasis. Dense deposit disease is a rare renal disease associated with mutations in Complement factor H and overactivity of the alternative complement pathway. As well as glomerulonephritis, many affected individuals have retinal drusen and may be at risk of vision loss due to macular atrophy or choroidal neovascularisation. We discuss the reclassification of dense deposit disease as a type of C3 glomerulonephropathy, and hypothesise on the mechanisms of retinal abnormalities. Drusen have also been described in individuals with other types of glomerulonephritis involving abnormalities of the classical (membranoproliferative glomerulonephritis type 1) or lectin (IgA nephropathy, lupus nephritis) complement pathways. Although drusen are found in abnormalities of all three complement pathways, the age at onset, aetiology, and the threat to vision differs. This review describes drusen and other retinal abnormalities associated with the glomerulonephritides due to abnormal activation in each of the three complement activation pathways, and provides the first report of drusen occurring in a patient with the recently reclassified C3 glomerulonephritis with homozygous variant V62I in complement factor H. Optometric management of young patients presenting with retinal drusen is discussed, and complement-based therapies for visual loss are reviewed.

KEYWORDS:

• C3 glomerulonephropathy
• complement
• drusen
• glomerulonephritis
• renal

Acknowledgments

We would like to thank the many individuals who have helped us better understand these diseases, and their clinicians who have referred them to us.

Research was conducted according to the Declaration of Helsinki as revised in 2013. All individuals whose retinal photographs are reproduced here have provided written informed consent for this.

Disclosure statement

HGM is a principal investigator for IONIS study NCT03815825 and has received speaker fees from IONIS. SFB is also an investigator for IONIS study.