• Multisystem autoimmune disease
• Chronic course with relapses and remissions
• Organ systems most frequently involved: skin, joints, kidneys, blood, and CNS
• Diverse manifestations in eye:
– Discoid lesions of eyelids
– Keratoconjunctivitis sicca (dry eye)
– Cranial neuropathy
– Optic neuropathy
– Retinal vasoocclusive disease
– Antimalarial drug toxicity
• Approximately 250,000 people have systemic lupus erythematosus (SLE) in the US (1)[B]
• Up to 1/3 of patients with SLE have ocular manifestations.
– Ocular surface disease: up to 30%
– Retinal manifestations: 3–30% (depends on systemic disease activity)
– Optic nerve involvement: 1%
• Gender: female 9:1
• Age: peak incidence 2nd–4th decade
• Race: African-American and Asian descent
• Family history
• Environmental factors: hormones, sunlight
• Drug-induced lupus: procainamide, hydralazine, quinidine, chlorpromazine, methyldopa, isoniazid
• Twin studies support genetic predisposition.
• Linkage studies have identified many candidate genes, particularly on chromosome 1q
• Associated with HLA-A1, HLA-B8, and HLA-DR3
• Autoimmunity may be triggered by autoantigen exposure during apoptosis.
– Autoantibody production
– Immune complex deposition
• Lupus retinopathy associated with immune complex–mediated arteriolar occlusion and thrombosis
COMMONLY ASSOCIATED CONDITIONS
• Secondary Sjögren’s syndrome
• Antiphospholipid antibody (APA) syndrome (found in 77% of SLE patients with retinal or optic nerve disease vs. 29% of other SLE patients) (2)[B]
SLE is diagnosed by at least 4 of the 11 following American College of Rheumatology (ACR) criteria:
• Malar rash
• Discoid rash
• Oral ulcers
• Serositis (pleuritis, pericarditis)
• Renal disorder (proteinuria or cellular casts)
• CNS disorder (seizures, psychosis)
• Hematologic disorder (anemia, leucopenia, thrombocytopenia, lymphopenia)
• Immunologic disorder
– Antidouble-stranded DNA (anti-dsDNA)
– False-positive RPR or VDRL
• Antinuclear antibody (ANA) positive
• Visual decline
• Ocular adnexa—edema, mass, proptosis
• Motility–-myositis, cranial neuropathy, intranuclear ophthalmoplegia
• Eyelids—discrete, scaly lesions (discoid lupus)
• Conjunctiva—inflammation (noninfectious conjunctivitis)
– Episcleritis (superficial, blanches with topical phenylephrine)
– Scleritis (deep, does not blanch with topical phenylephrine, nodular or diffuse, anterior or posterior)
– Reduced tear film, punctate keratopathy, filaments (dry eye, Sjögren’s syndrome)
– Interstitial keratitis (rare)
– Peripheral ulcerative keratitis (rare)
– Vortex keratopathy (verticillata)
Associated with antimalarial drug use
Rarely visually significant
Reversible with cessation of treatment
• Anterior chamber
– Cell and flare (iritis)
– Hypopyon uveitis (rare)
• Lens (cataract)
– Especially posterior subcapsular
– Associated with chronic steroid use
• Vitreous—inflammation (posterior uveitis)
– Lupus retinopathy
– Cotton–wool spots (nerve fiber layer infarcts)
– Intraretinal hemorrhages
– Vascular tortuosity
– Vasoocclusive retinopathy (more severe)
– Capillary nonperfusion
– BRVO, CRVO, BRAO, CRAO
– Neovascularization of disc and retina
– Vitreous hemorrhage
– Traction retinal detachment
– Uveal effusion
– Serous retinal detachment
– Choroidal infarction
– Choroidal neovascular membrane
– Optic nerve
– Papilledema (intracranial hypertension)
DIAGNOSTIC TESTS & INTERPRETATION
Initial lab tests
• Anti-dsDNA (highly specific)
• ANA (sensitive)
Follow-up & special considerations
• Other autoantibodies
– APA (anticardiolipin and lupus anticoagulant)
– Anti-N-methyl-d-aspartic acid (NMDA)
– Anti-alpha actinin
• Fluorescein angiography to assess retinal and choroidal circulation
– ICG to assess choroidal circulation
– OCT to assess for macular edema or serous retinal detachment
– B-scan ultrasonography to assess vitritis and for retinal detachment
Follow-up & special considerations
Retinal vasculitis is associated with CNS lupus involvement. Consider CNS imaging with MRI/magnetic resonance angiography (MRA) to evaluate for thrombotic events.
• Biopsies of eyelid lesions show immunoglobulin deposition at the junction of epidermis and dermis on immunohistochemical staining.
• Orbital and adnexal involvement can also be confirmed by biopsy.
• Discoid lupus on the eyelids should be distinguished from blepharitis.
• Optic neuritis in SLE can resemble demyelinating disease but is often more severe.
• Lupus retinopathy resembles diabetic and hypertensive retinopathy.
• Patients with SLE on immunosuppressive therapy often present with new ocular complaints. It is important to rule out an infectious etiology before continuing or accelerating immunosuppressive therapy. Consider:
– Herpetic retinitis (herpes simplex virus [HSV], herpes zoster virus [HZV], cytomegalovirus [CMV])
– Lyme disease
• Artificial tears for episcleritis, dry eye
• Oral prednisone for more severe ocular manifestations: 1–2 mg/kg/day
• Nonsteroidal anti-inflammatory drugs (NSAIDs)
• Steroid-sparing immunosuppressive agents:
– Mycophenolate mofetil
• Intravenous immunoglobulins
• Newer biologic agents:
– Rituximab (Rituxan)
– Anticytokine agents
Care should be taken to prevent and manage side effects of immunosuppressive therapy such as gastric prophylaxis, blood sugar and blood pressure monitoring, and purified protein derivative (PPD) tuberculosis screening.
Issues for Referral
Systemic treatment of ocular manifestations should be comanaged with the patient’s primary doctor and/or rheumatologist.
• Anticoagulation for vasoocclusive disease or APA syndrome
• Treat complications of proliferative retinopathy:
– Panretinal photocoagulation
Consider inpatient admission for pulse IV methylprednisolone: 1g/day
• The antimalarial agents are associated with bull’s eye maculopathy leading to impairment of visual acuity, color vision, and visual field.
• All patients initiating antimalarial therapy should receive counseling about risk of retinopathy and have baseline eye exam: visual acuity, dilated fundus examination, Amsler, Humphrey 10-2, optional tests (color, fundus photos, fluorescein angiography, multifocal electroretinogram [ERG])
• Risk factor for complications include dose >6.5 mg/kg hydroxychloroquine, >3 mg/kg chloroquine, duration >5 years, renal or liver disease, preexisting retinal disease, and age >60 years.
– Low-risk patients do not require additional screening exams.
– High-risk patients should have annual screening exams.
• Cessation of treatment may halt or even reverse sight-threatening complications.
• Vision loss in 55% of patients with severe vasoocclusive retinopathy (4)[B]
• Optic neuritis outcomes highly variable, appear to improve with early initiation of steroid treatment (5)[B]
Visual loss, retinal detachment, optic neuropathy
1. Helmick CG, Felson DT, Lawrence RC, et al. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part I. Arthritis Rheum 2008;58(1):15–25.
2. Montehermoso A, Cervera R, Font J, et al. Association of antiphospholipid antibodies with retinal vascular disease in systemic lupus erythematosus. Semin Arthritis Rheum 1999;28:326–332.
3. Marmor MF, Carr RE, Easterbrook M, et al. Recommendations on screening for chloroquine and hydroxychloroquine retinopathy. A report by the American Academy of Ophthalmology. Ophthalmology 2002;109:1377–1382.
4. Jabs DA, Fine SL, Hochberg MC, et al. Severe retinal vaso-occlusive disease in systemic lupus erythematosus. Arch Ophthalmol 1986;104: 558–563.
5. Lin YC, Wang AG, Yen MY. Systemic lupus erythematosus-associated optic neuritis: clinical experience and literature review. Acta Ophthalmol 2009;87(2):204–210.