SLE may affect any structure of the eye and its adnexae, and ocular involvement has been reported to occur in up to one-third of patients [15].

Lupus may result in periorbital skin involvement occurring as an extension of the characteristic malar rash seen in the condition. In addition, discoid lupus may primarily affect the lids, presenting as a chronic, intractable blepharitis, or as raised scaly lesions typically affecting the lateral third of the lower lids [16, 17].

Keratoconjunctivitis sicca (KCS) is the most common ocular manifestation of SLE, occurring in up to one-third of patients [15]. KCS is associated with the HLA-DRW52 antigen and anti-Ro (SSA) and anti-La (SSB) antibodies [18]. Affected patients demonstrate typical stippling of the corneal and conjunctival epithelia with fluorescein and Rose Bengal stains, as well as abnormal Schirmer testing. Filamentary keratitis and fibrosis of the corneal stroma and conjunctiva may occur in severe cases [19, 20]. Scleritis and episcleritis are less common manifestations of SLE, with lupus being responsible for 4 % of cases of scleritis, and 11 % of cases episcleritis in some studies [21, 22]. The presence of scleritis may also be an indicator of systemic disease activity [23]. Peripheral ulcerative keratitis, interstitial keratitis, and anterior uveitis are less common manifestations of SLE, but should always be considered in the differential diagnosis of these conditions [24, 25].

Retinal involvement is the second most common ophthalmic manifestation of lupus, occurring in some studies in 3–29 % of patients [26]. Retinal vascular changes have been shown to correlate with systemic disease activity, and the waxing and waning of retinal lesions parallels the course of the systemic disease [27]. In one prospective study of patients with lupus retinopathy, 88 % of patients had active systemic disease, 73 % had active CNS involvement, and patients with retinal involvement had a higher mortality rate compared to patients without retinal involvement [28]. The most common retinal manifestations of SLE are cotton wool spots and intraretinal hemorrhages [29]. In patients with retinal vascular involvement, lupus typically results in an arteriolitis, and although venular inflammation may occur, the latter is a less common manifestation of the disease. Vasculitis will manifest as vascular tortuosity and sheathing. Other findings may include microaneurysms, retinal edema, and exudates [19, 26, 30]. A less common but more destructive complication is severe vaso-occlusive retinopathy, a syndrome which occurs as a consequence of severe, widespread arteriolitis and venulitis resulting in multiple branch retinal artery occlusions, extensive capillary non-perfusion, and if untreated, may culminate in retinal neovascularization and vitreous hemorrhage, with associated poor visual prognosis [31, 32]. Patients with antiphospholipid antibodies such as lupus anticoagulant and anti-cardiolipin antibodies are at a higher risk of developing severe vascular occlusive disease [33, 34].

Choroidal involvement is also highly correlated with systemic disease activity, and may result in fluid accumulation beneath the neurosensory retina and retinal pigment epithelium, and progress to large exudative retinal and RPE detachments [35–37]. Uveal effusions have also been reported in SLE, and may lead to secondary angle closure glaucoma [38].

Central nervous system involvement in SLE may result in cranial nerve palsies, as well as optic neuritis, the latter of which may occur with transverse myelitis [39, 40]. Anterior ischemic optic neuropathy, as well as chiasmal and retrochiasmal inflammation are other neuro-ophthalmic manifestations of the disease [41].

Lupus may, in addition, result in orbital inflammation, which may manifest as periorbital edema, panniculitis, trochleitis, orbital myositis and orbital infarction [42–47].

The pathogenesis of SLE is incompletely understood, and the disease is thought to occur as a consequence of environmental factors in genetically predisposed individuals. A genetic susceptibility to lupus is evidenced by the increased risk in siblings of patients with SLE of developing the disease, the concordance rate of 24 % for identical twins, and the association with the major histocompatibility genes HLA-DR2, DR3, B7, and B8 [48]. In addition to genetic factors, both patient and external environmental factors, such as sunlight exposure, endogenous estrogen production, hormone replacement therapy, Epstein–Barr virus infection, and defective clearance of apoptotic cells resulting in the release of autoantigens, are thought to play a role in the pathogenesis of the disease [6, 49–52]. Other factors, including deficiency in components of the classical complement pathway, mannan-binding protein deficiencies, and genetic polymorphisms in cytokines, such as TNF-α and IL-6 have also been implicated in the underlying immune dysregulation that occurs in SLE, resulting in suppressor T-cell dysfunction, B-cell hyperreactivity, polyclonal B-cell activation, and autoantibody production [53–55].

Such autoantibody production includes, among others, those directed against nuclear antigens, such as the anti-single-stranded and double-stranded DNA antibodies, as well as those against annexins, Ro, La, CD45 cell surface glycoprotein, and histones [6, 48, 56, 57]. These antibodies result in tissue damage by the Coombs and Gell Type II hypersensitivity reaction, with direct toxic effects on targeted cells, resulting in thrombocytopenia, hemolytic anemia, and CNS disease from antiplatelet, anti-red blood cell and antineuronal antibodies, respectively [48]. Type III hypersensitivity reactions, with antigen-antibody deposition, are thought to be responsible for renal dysfunction as well as the ocular manifestations of lupus, and such immune complexes have been identified in retinal and cerebral endothelium, ciliary body, choroid, and conjunctival basement membrane [58]. Such immune complex deposition activates the complement cascade by the classical pathway, resulting the C3a and C5a mediated chemotaxis, and the release of hydrolytic enzymes and proinflammatory cytokines by neutrophils, resulting in tissue damage [48, 59].

The diagnosis of lupus is based on a combination of clinical features and immunologic tests. It should be kept in mind, however, that ocular involvement may be the first manifestation of SLE in some patients [23]. In addition, ocular manifestations are not included in the ACR or SLICC diagnostic criteria, and although such criteria are useful in identifying patients in a clinical research setting, a diagnosis of SLE can be made and treatment initiated even if not all criteria are met [23]. More than 95 % of patients demonstrate antinuclear antibody (ANA) production, and the test is an effective screening tool for SLE. However, it is nonspecific, and additional testing for anti-double-stranded DNA, Smith antigen, and anti-Ku, and anti-PCNA/cyclin are more specific for the disease [60]. Low levels of C3 and C4 occur in patients with active SLE.

In patients with suspected keratoconjunctivitis sicca, fluorescein and Rose Bengal staining, and Schirmer testing are useful in determining the underlying mechanism of dry eye. Keratoconjunctivitis sicca associated with SLE is typically associated with aqueous deficiency rather than evaporative dry eye syndrome [1].

Fluorescein angiography is a valuable tool in detecting subtle retinal vasculitis, as well as retinal ischemia, edema and neovascularization, and is useful in gauging retinal vasculitic disease activity [26]. Magnetic resonance imaging with contrast in patients with optic nerve involvement may help differentiate lupus optic neuritis from anterior ischemic optic neuropathy, as most patients with neuritis demonstrate enhancement of the optic nerve [61].

Patients with lupus and ocular involvement require systemic therapy to control disease activity. In individuals with arthritis, serositis, and dermatologic manifestations without additional systemic involvement, oral nonsteroidal anti-inflammatory drugs (NSAIDs) or aminoquinolines, such as chloroquine or hydroxychloroquine, with careful monitoring for associated retinopathy, may be adequate to control disease activity [62, 63]. However, barring patients with mild keratoconjunctivitis sicca, individuals with ocular involvement typically require initial therapy with systemic corticosteroids, either oral, or intravenous, followed by systemic steroid-sparing immunomodulatory therapy. This typically includes the use of cyclophosphamide, mycophenolate mofetil, azathioprine, or methotrexate [62, 64].

Cyclophosphamide, an alkylating agent that causes cross-linking of DNA bases, inhibits the rapid proliferation of lymphocytes, and has a long track record of safety and efficacy in patients with SLE, particularly lupus nephritis, as well as in patients with severe ocular involvement [65, 66]. Mycophenolate mofetil is an inhibitor of inosine monophosphate dehydrogenase, an enzyme involved in purine synthesis, and has also been shown to be effective, with one meta-analysis suggesting superiority to cyclophosphamide in patients with lupus nephritis [67]. Azathioprine, a prodrug that is converted to 6-mercaptopurine, is also an inhibitor of purine synthesis with proven efficacy in systemic SLE, including patients with ocular involvement [68]. Rituximab is a monoclonal anti-B lymphocyte antibody that may be effective in controlling inflammation patients with recalcitrant SLE, and case reports suggest it may be useful in selected patients with associated retinal vasculitis and optic neuritis [69, 70]. Belimumab, another recently developed biologic response modifier, is a monoclonal antibody to B-cell activating factor (BAFF). It was the first biologic response modifier approved for SLE, receiving FDA approval in 2011 [71, 72]. Although Phase III trials demonstrated modest efficacy in patients with active lupus, its role in patients with ocular involvement remains to be seen [71, 73]. In patients with severe, recalcitrant uveitis, plasmapheresis has been shown to decrease inflammation and improve vision in selected cases [74].

The 5-and 10-year survival rates in patients with lupus have improved significantly with the advent of steroid-sparing immunomodulatory therapy, and currently exceed 85 % [75]. With appropriate therapy, the majority of patients with ocular involvement have a good visual prognosis, including most patients with retinal manifestations [26, 28]. However, patients with widespread retinal occlusive disease have a much poorer prognosis, with over half of patients in one study having a final visual acuity of worse than 20/200 [31].

SLE is a chronic, multisystem autoimmune disorder that can affect almost any ocular and adnexal structure. End-organ damage occurs as a result of autoantibody production resulting in direct cytotoxicity as well as immune complex deposition. Systemic disease activity has been shown to correlate with the activity of retinal vascular manifestations. With appropriate therapy, most patients with ocular involvement have a good visual prognosis. However, patients with severe occlusive retinopathy are at higher risk systemic morbidity and severe vision loss.