Systemic Lupus Erythematosus and the Eye

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder that affects approximately 5 per 100,000 persons per year in the United States, and roughly half as many in Europe and Japan.^1,2 Women develop SLE nine times more often than men, with a particularly high incidence in those of Afro-American and Afro-Caribbean descent. The clinical course, which can vary dramatically from patient to patient, is most frequently relapsing-remitting or chronic. While the pathogenesis of SLE is multifactorial and incompletely understood, both genetic susceptibility and the formation of a wide array of autoantibodies with the subsequent deposition of immune complexes appear to play important roles in most manifestations. Secondary, immune-mediated hematologic, renal, central nervous system, and cardiovascular complications occur frequently and contribute meaningfully to disease-related morbidity and mortality.³

Ocular involvement occurs in up to one-third of patients with active SLE,^4–11 with the most frequent complications including keratoconjunctivitis sicca, episcleritis/scleritis, and lupus retinopathy. More extensive ischemic retinal¹² and choroidal vasculitis - the latter often presenting as serous retinal detachment,^13–15 are less common, but can be blinding and point to the potential presence of active systemic disease. Ocular complications related to treatment, particularly with corticosteroids¹⁶ and hydroxychloroquine,¹⁷ are also well recognized. One original article¹⁸ and two letters^19,20 in this issue of Ocular Immunology & Inflammation address various aspects of the diagnosis and management of ocular involvement by SLE.

Dammacco et al.¹¹ described the ocular complications of both SLE and medications used to treat this condition in 98 patients seen at two referral centers in Bari, Italy. The diagnosis of SLE was based on the revised criteria of the American College of Rheumatology (ACR) and disease classification was based on criteria from the Systemic Lupus International Collaborating Clinics (SLICC). All patients were Caucasian and 90 (91.8%) were female. Follow-up ranged from 1.5 to 12.4 years and was longer than 10 years in 62% (mean 3.8 ± 1.7 years). Age ranged from 14 to 69 years (mean 31 ± 11 years). The median time from the onset of first symptoms to the diagnosis of SLE was 11 months. Thirteen patients had no eye examination at the time of SLE diagnosis. Overall, 29 subjects (29.6%) had one or more ocular finding. These included keratoconjunctivitis sicca (11.2%), scleritis (3.1%), discoid lesions on the eyelid (2.0%), Purtsher-like retinopathy (1.0%), and central retinal artery occlusion in the setting of associated antiphospholipid syndrome (1.0%). Over the variable course of follow-up virtually all patients were on systemic glucocorticoids (0.01–1.0 mg/kg/day) and hydroxychloroquine (HCG; 200 mg/daily). Non-corticosteroid immunosuppressive drugs were used more selectively. Corticosteroid-induced cataracts where identified in 21.4% of patients, whereas corticosteroid-induced ocular hypertension/glaucoma developed in 4.1%. Two patients (2.0%) developed diabetic macular edema in the setting of corticosteroid-induced diabetes mellitus. Hydroxychloroquine-induced vortex keratopathy and toxic maculopathy were uncommon, with each occurring in one patient (1.0%). The authors acknowledged the limitations inherent in the retrospective, single-center nature of their study cohort.²¹ While the prevalence of ocular complications of both SLE and of glucocorticoids and HCQ were lower than reported in some clinic-based cohorts, perhaps related to increased use of non-corticosteroid immunosuppressive agents, the authors stressed the importance of both baseline and routine ophthalmologic examinations as part of the multidisciplinary approach to patients with this disorder.

Zhang et al.¹⁹ described the occurrence of bilateral hemorrhagic retinopathy in a 15-year-old Asian girl in Shanghai, China, following self-discontinuation of maintenance prednisolone and azathioprine. Best-corrected vision at presentation was 20/40 on the right and 20/20 on the left. Ophthalmoscopic and optical coherence tomography examinations revealed bilateral sub-retinal, pre-retinal, and intraretinal hemorrhages, some of which had white centers typical for Roth spots. Laboratory testing revealed profound thrombocytopenia, which was treated with platelet transfusion, intravenous immunoglobulin, and high-dose intravenous methylprednisolone with improvement. The authors emphasized that Roth spots, while typical for endocarditis and hematologic malignancies, may occur infrequently in patients with SLE.²²

Lee et al.²⁰ described a 34-year-old Malay women with severe SLE who developed sudden painless loss of vision to counting fingers with an afferent pupillary defect in one eye. Indocyanine green angiography (ICGA) revealed evidence of choroidal ischemia due to SLE-induced vasculitis. Ophthalmoscopic and fluorescein angiographic examinations showed several intraretinal hemorrhages and areas of retinal pigment epithelial disruption, but were otherwise unremarkable. The authors reminded us that serous retinal detachment is the most common manifestation of SLE-associated choroiditis and emphasized the importance of ICGA for documenting the location and extend of choroidal vasculitis and/or ischemia.^14,15,23

Together, these studies highlight the diverse array of complications associated both with SLE and its most common treatments - systemic corticosteroids and HCQ. While ocular involvement occurs in up to one-third of patients with SLE, and all patients with SLE should undergo both baseline and periodic eye examinations, it is important to remember that lupus is a relatively uncommon cause of uveitis. In fact, a recent comprehensive review of reported series from uveitis clinics suggested that SLE accounted for less than 0.5% of cases in the referral setting.²⁴ Routine antinuclear antibody (ANA) testing in all patients with ocular inflammation is not recommended, therefore, unless specific signs or symptoms suggestive of lupus are present.^24–26 Ocular findings that might prompt ANA and broader SLE testing in adults with ocular inflammation include keratoconjunctivitis sicca, episcleritis/scleritis, hemorrhagic or ischemic retinopathy, and serous retinal detachment. In contrast, children with anterior uveitis should undergo routine antinuclear antibody testing to screen for juvenile idiopathic arthritis.^25,27

Acknowledgments

Supported in part by The Pacific Vision Foundation (ETC) and The San Francisco Retina Foundation (ETC).

Additional information

Funding

The authors have no relevant financial conflicts.