Systemic Lupus Erythematosus and the Eye

Systemic lupus erythematosus is an autoimmune multisystem disease with immune complex deposition, complement activation and vasculopathy. Ocular disease occurs in about one third of patients, mostly dry eye, but the retinal and optic nerve manifestations signal active systemic disease.

• Lupus retinopathy (cotton wool spots, haemorrhages) reflects active disease and is associated with nephritis, hypertension and central nervous system involvement. The vaso occlusive form is strongly associated with antiphospholipid antibodies and carries a poor visual outlook.
• Choroidopathy, optic neuropathy and scleritis indicate severe disease and warrant intensive systemic immunosuppression.
• Hydroxychloroquine is the foundation of lupus treatment, so ocular toxicity monitoring is part of routine lupus care.

• Eyelids and skin: discoid lupus plaques of the lids with scarring, lash loss and depigmentation, and periorbital oedema (nephritis).
• Dry eye (keratoconjunctivitis sicca) in up to a third, with secondary Sjogren overlap, filamentary keratitis and punctate keratopathy.
• Episcleritis and scleritis (diffuse, nodular, rarely necrotising or posterior).
• Retinopathy: cotton wool spots, intraretinal haemorrhages, microaneurysms and hard exudates in a mild nonocclusive pattern, often asymptomatic.
• Vaso occlusive retinopathy: arteriolar occlusion, branch or central retinal artery or vein occlusion, extensive capillary nonperfusion, retinal neovascularisation, vitreous haemorrhage and tractional detachment.
• Lupus choroidopathy: multifocal serous detachments of the retina and retinal pigment epithelium with choroidal infarcts, typically in patients with nephritis, malignant hypertension or thrombotic microangiopathy.
• Optic neuropathy: optic neuritis (with severe visual loss and little recovery), ischaemic optic neuropathy, and chiasmal or retrochiasmal lesions from cerebral vasculitis or infarction (homonymous hemianopia).
• Neuro ophthalmic: cranial nerve palsies (sixth, third), nystagmus, internuclear ophthalmoplegia, transient visual loss (amaurosis) from antiphospholipid thromboembolism, and idiopathic intracranial hypertension.
• Orbital: myositis, dacryoadenitis and orbital pseudotumour pattern.
• Drug effects: hydroxychloroquine retinopathy (bull's eye maculopathy, parafoveal ring scotoma), steroid cataract and glaucoma, and rare chloroquine corneal verticillata.

• Ocular: slit lamp, tear film assessment, dilated fundus examination, fluorescein angiography (nonperfusion, vasculitis, choroidal leakage), OCT (macular oedema, subretinal fluid, thickened choroid), OCT angiography, visual fields, pupillary examination and colour vision, visual evoked potentials in optic nerve disease.
• Serology: anti-nuclear antibody (positive in more than 95 percent), anti-double-stranded DNA and anti-Smith antibodies, complement C3 and C4 (low in active disease), antiphospholipid antibodies (lupus anticoagulant, anticardiolipin IgG and IgM, anti-beta-2 glycoprotein I), ESR and CRP, full blood count (cytopenias), urinalysis with protein-to-creatinine ratio and renal function.
• Neuroimaging: MRI brain and orbits with contrast and MR angiography for optic neuropathy and cerebrovascular disease.
• Blood pressure measurement at each visit, since hypertension drives choroidopathy and retinopathy.
• Screening for hydroxychloroquine retinopathy: baseline within the first year, then annually from 5 years (annually from the start in those with renal disease, tamoxifen use or doses over 5 mg/kg), using OCT, automated visual fields (10-2, or 24-2/30-2 in Asian patients) and fundus autofluorescence.

• Baseline for all patients: hydroxychloroquine 200 to 400 mg daily, not exceeding 5 mg/kg/day of real body weight, with dose reduction when eGFR falls. It reduces flares, thrombosis and organ damage.
• Dry eye: preservative free tears 4 to 8 times daily, ointment at night, punctal plugs, ciclosporin 0.05% twice daily, autologous serum drops.
• Discoid eyelid lesions: sun protection, topical corticosteroid or tacrolimus 0.1% ointment, and systemic hydroxychloroquine.
• Scleritis: oral NSAID (flurbiprofen 100 mg three times daily or naproxen 500 mg twice daily) with gastric protection, then oral prednisolone 0.5 to 1 mg/kg/day if inadequate, and a steroid sparing agent (mycophenolate mofetil 1 g twice daily or azathioprine 2 mg/kg/day). Necrotising scleritis requires pulse therapy.
• Active retinopathy or choroidopathy: control of blood pressure to below 130/80 mmHg and treatment of nephritis. Oral prednisolone 0.5 to 1 mg/kg/day. For retinal vasculitis, optic neuritis or any sight threatening disease: intravenous methylprednisolone 500 to 1000 mg daily for 3 days, followed by oral prednisolone with taper.
• Immunosuppressant for severe or steroid dependent disease: cyclophosphamide intravenously 500 to 1000 mg/m2 monthly for 6 months (or 500 mg every 2 weeks for 6 doses), mycophenolate mofetil 1 to 1.5 g twice daily, azathioprine 2 mg/kg/day, rituximab 1000 mg intravenously on days 1 and 15, or belimumab 10 mg/kg intravenously at weeks 0, 2 and 4 and then every 4 weeks.
• Antiphospholipid related vaso occlusion (arterial or venous): long term anticoagulation with warfarin to an INR of 2 to 3 (3 to 4 for recurrent arterial events), with low dose aspirin 75 mg added in selected arterial events. Direct oral anticoagulants are not used in triple positive antiphospholipid syndrome.
• Retinal neovascularisation: panretinal photocoagulation (1200 to 1600 spots, 500 micrometres, 0.1 s) and intravitreal anti-VEGF (bevacizumab 1.25 mg, ranibizumab 0.5 mg or aflibercept 2 mg). Vitrectomy for nonclearing vitreous haemorrhage over 3 months or tractional detachment.
• Optic neuritis or ischaemic optic neuropathy: pulse methylprednisolone within days, and early cyclophosphamide or rituximab if vision does not improve, since delay lowers the chance of recovery.
• Choroidal serous detachment: management of the underlying hypertension and nephritis; the retinal detachment resolves as systemic disease is controlled.
• Hydroxychloroquine toxicity: stop the drug when screening shows early changes (loss may progress for months after cessation), and coordinate an alternative with the rheumatologist.
• Steroid complications: IOP checks at every visit while on prednisolone, cataract surgery when vision limiting, and bone protection.
• Review every 3 to 6 months when disease is active, and urgent review for any new visual symptom.