Retinal Drusen Are More Common and Larger in Systemic Lupus Erythematosus With Renal Impairment

Ye Ji Ham; Eleanor Nicklason; Tony Wightman; Sarah Akom; Kieran Sandhu; Philip Harraka; Deb Colville; Andrew Catran; David Barit; David Langsford; Tim Pianta; Andrew Foote; Russell Buchanan; Heather Mack; Judy Savige

doi:10.1016/j.ekir.2022.01.1063

Retinal Drusen Are More Common and Larger in Systemic Lupus Erythematosus With Renal Impairment

Kidney Int Rep. 2022 Feb 2;7(4):848-856. doi: 10.1016/j.ekir.2022.01.1063. eCollection 2022 Apr.

Authors

Affiliations

¹ The University of Melbourne Department of Medicine, Northern Health and Melbourne Health, Melbourne, Australia.
² Renal Unit, Northern Health, Melbourne, Australia.
³ Rheumatology Unit, Northern Health, Melbourne, Australia.
⁴ The University of Melbourne Department of Ophthalmology, The Royal Victorian Eye and Ear Hospital, East Melbourne, Australia.

Abstract

Introduction: Complement has been implicated in systemic lupus erythematosus (SLE) pathogenesis on the basis of the associations with inherited complement defects and genome-wide association study risk alleles, glomerular deposits, reduced serum levels, and occasional reports of retinal drusen. This study examined drusen in SLE and their clinical significance.

Methods: This cross-sectional observational study compared individuals with SLE recruited from renal and rheumatology clinics with hospital controls. Participants were reviewed for clinical features and underwent imaging with a nonmydriatic retinal camera. Deidentified images were examined by 2 trained graders for drusen number and size using a grid overlay.

Results: The cohort with SLE (n = 65) comprised 55 women (85%) and 10 men (15%) with a median age of 47 years (interquartile range 35-59), where 23 (35%) were of southern European or Asian ancestry, and 32 (49%) had biopsy-proven lupus nephritis. Individuals with SLE had higher mean drusen numbers than controls (27 ± 60, 3 ± 9, respectively, P = 0.001), more drusen counts ≥10 (31, 48% and 3, 5%, respectively, P < 0.001), and more medium-large drusen (14, 22% and 3, 5%, respectively, P < 0.001). In SLE, mean drusen counts were higher, and drusen were larger, with an estimated glomerular filtration rate (eGFR) <90 ml/min per 1.73 m² (P = 0.02, P = 0.02, respectively) or class IV nephritis (P = 0.03, P = 0.02).

Conclusion: Drusen composition resembles that of glomerular immune deposits. CFH controls complement activation in the extracellular matrix and CFH risk variants are shared by drusen in macular degeneration and by SLE. CFH represents a possible treatment target for SLE especially with renal impairment.

Keywords: SLE; complement; drusen; immune complexes; impaired kidney function; lupus nephritis.