Posterior Ocular Manifestations

Systemic lupus erythematosus can affect many ocular and adnexal structures. Ocular manifestations tend to occur in patients who have active

systemic disease (Table 18.2) [17, 18]. Retinal involvement is the second most common (after keratoconjunctivitis sicca) ophthalmological manifestation in SLE, [19] the incidence varies between 3.3% and 28.1%, and the appearance

Fig. 18.3 Cotton-wool spots and retinal hemorrhages are the most frequently reported ophthalmic findings in systemic lupus erythematosus (left). Disappearance of retinal lesions after systemic disease improvement (right)

(Reprinted with permission from Arévalo JF, Lowder CY, Muci-Mendoza R. Ocular manifestations of systemic lupus erythematosus. Curr Opin Ophthalmol 2002, 13:404–410.)

and disappearance of some of the retinal lesions parallel the course of systemic disease [17–20].

Mild Retinopathy

Most patients with mild retinopathy are at low risk of vision loss [19, 21]. Cotton-wool spots and retinal hemorrhages (Fig. 18.3) are the most frequently reported findings, but retinal edema, hard exudates, microaneurysms, arterial narrowing, venous engorgement, and vascular tortuosity have also been noted [17, 18]. Although many of these changes are part of the clinical picture of hypertensive retinopathy and hypertension is often present secondary to lupus renal disease, lupus retinopathy can occur as an independent manifestation of the underlying disease process in the absence of hypertension [17, 18]. Fluorescein angiography demonstrates capillary non-perfusion, vascular incompetence and fluorescein leakage even in eyes that appear clinically normal in patients with both active and mildly active disease [18].

The retinal microangiopathy associated with SLE is thought to be due to widespread immune complex deposition with resultant vasculitis, endothelial damage, and vessel leakage or microvascular thrombosis [21–23]. Although anticardiolipin antibodies or lupus anticoagulant may play a

critical role in some patients, their precise role in this process is uncertain [22, 24]. It is felt that accelerated atherosclerosis as a result of hypertension, steroid use, and dyslipidemia in SLE may have a role in the development of this form of retinopathy [19, 25, 26]. Due to the fact that appearance and disappearance of retinal lesions parallel the course of systemic disease, the effective treatment of SLE and any associated systemic hypertension results in concurrent decrease in some of the retinal lesions, specially the disappearance of cotton-wool spots (see Fig. 18.3) [17, 19].

Vaso-occlusive Retinopathy

Severe vaso-occlusive retinopathy is a rare form of retinopathy in SLE often associated with poor visual prognosis and neovascularization. It is associated with antiphospholipid antibodies, which are thrombogenic and are associated with both central nervous system (CNS) and vasoocclusive phenomena [27]. According to Montehermoso et al. [28], antiphospholipid antibodies were found in 77% of patients with lupusrelated retinal or optic nerve disease, compared with only 29% of SLE patients without such ocular involvement. There is a strong association between this severe form of retinopathy and central nervous system manifestations of SLE [27, 28].

Fig. 18.4 Branch retinal arteriole occlusion and consequent retinal infarction

Fig. 18.5 Upper branch retinal vein occlusion with superficial retinal hemorrhages in resolution. See the difference between the upper tortuous and dilated veins against the normal inferior retinal veins

This form of retinopathy is typically characterized by occlusion of retinal arterioles and consequent retinal infarction (Fig. 18.4). Proliferative retinopathy with severe vaso-occlusive disease can occur in up to 40% of patients; poor visual outcomes with visual loss have been reported in 80% of these cases [26] and are often related with vitreous hemorrhage, retinal traction, and retinal detachment. Fluorescein angiography demonstrates arterial and capillary non-perfusion, leakage from neovascular fronds, and staining of the walls of involved vessels. Other retinal presentations include large vessel occlusions (central and branch retinal vein occlusions (Fig. 18.5) and central and branch retinal arteriole occlusions) (see Fig. 18.4). Central retinal vein occlusion appears to be less common than arterial occlusive disease [17, 18]. Some patient’s retinopathy may resemble that seen in patients with retinitis pigmentosa because previous vascular occlusive disease resulted in retinal mottling and large clumps of pigment. In the immunosuppressed state, rare retinal infections may occur: retinal necrosis due to herpes simplex, varicella zoster, and cytomegalovirus are all reported [27, 29].

The histopathological findings include perivascular lymphocytic infiltrates, endothelial swelling, and thrombus formation, with occlusion of retinal and choroidal vessels, including the choriocapillaries [29]. Complete agreement

has not been reached concerning the medical treatment of ocular thrombotic disease in SLE. Anticoagulant therapy is generally recommended (particularly when APAs are present), and the addition of an antiplatelet drug such as low dose of acetylsalicylic acid may be beneficial. The role of immunosuppressive agents in preventing the thrombotic complications remains unclear. These drugs should probably be given to patients with severe and progressive lesions that compromise the visual prognosis. Initial treatment is usually with oral corticosteroids (e.g., prednisolone 1 mg/kg/ day), but may be preceded by intravenous methylprednisolone (e.g., 500 mg/1 g daily for 3 days). This is then supplemented with, or replaced by, other immunosuppressive agents as part of a steroid-sparing strategy or for resistance disease [27]. Proliferative retinopathy usually requires treatment with laser (panretinal photocoagulation) similar to the treatment for proliferative diabetic retinopathy [25, 27].

Lupus Choroidopathy

Although lupus choroidopathy is less common than retinopathy, its presence is well recognized and usually suggests active systemic vascular disease [27]. It typically manifests as multifocal serous detachments of the retina and underlying retinal pigment epithelium (RPE) (Fig. 18.6),

Fig. 18.6 Lupus choroidopathy characterized by multifocal retinal pigment epithelium detachments. Note the cotton wool spot (Reprinted with permission from Arévalo JF, Lowder CY, MuciMendoza R. Ocular manifestations of systemic lupus erythematosus. Curr Opin Ophthalmol. 2002, 13:404–410)

Fig. 18.7 Central serous chorioretinopathy. (a) Color picture showing an area of round subretinal fluid involving the fovea. (b) Fluorescein angiography showing a focal

site or leakage from the choroid into the subretinal space with fluorescein pooling

sometimes progressing to large, exudative retinal detachments [30, 31]. Typical central serous chorioretinopathy has been described (Fig. 18.7) [31]. Other complications include choroidal effusions (which have been reported to cause secondary angle closure) [32], choroidal infarction or ischemia, choroidal neovascular membranes [33], and choroidal infections [34, 35]. Fluorescein angiography demonstrates focal or multiple sites of ischemia or leakage from the choroid into the sub-RPE and subretinal spaces (Fig. 18.8) [23]. Indocyanine green angiography (ICG) can provide information that is not detectable by clinical or fluorescein angiographic examination in patients with systemic

lupus choroidopathy. ICG may reveal early focal areas of transient choroidal indocyanine green hypofluorescence suggesting choroidal filling delay, fuzziness of large choroidal vessels probably caused by choroidal vessel wall damage, with abnormal diffusion and retention of the indocyanine green molecule in the choroidal stroma and poorly defined areas of indocyanine green hypofluorescence suggesting vascular obstruction of the fenestrated choriocapillaris or choroidal stromal atrophy [36]. According to Gharbiya, [36] these three features are all nonspecific and are seen in other inflammatory or noninflammatory ocular and systemic diseases involving the choroid,

Fig. 18.8 (a) Central and (b) peripheral ocular fundus color pictures with a whitish superotemporal streak of choroidal infarction. (c) Early venous phase of the

fluorescein angiogram showing multiple sites of choroidal ischemia. (d) Focal leakage from the choroid into the subretinal space in the late frames of the angiogram

including central serous chorioretinopathy. However, the presence of a focal cluster of pinpoint spots of ICG choroidal hyperfluorescence, appearing from the intermediate to late phases, may represent immune deposits at the level of the choroidal stroma, Bruch’s membrane, or RPE’s basement membrane, containing immunoglobulins and leukocytes, which have been shown to bind the indocyanine green molecule.

The pathogenesis of lupus choroidopathy remains still unclear. Choroidal vascular damage and/or occlusion can produce multifocal serous retinal and RPE detachments; immune complex deposition in the choriocapillaris or autoantibody directed against the RPE has been hypothesized [30, 36]. An associated hypertension, resulting from lupus nephritis and corticosteroid therapy, can contribute to vessel wall damage due to increased hydrostatic pressure which forces fluid and blood cells out of the intravascular compartment

into surrounding tissues [30]. Thus, choroidal vasculopathy associated with systemic lupus erythematosus may be secondary to vasculitis, systemic hypertension, and corticosteroid therapy or probably to a variable combination of these processes [36]. Histopathology of SLE choroidopathyrevealsmassivemononuclearinfiltration, diffuse thickening of medium-sized choroidal vessels, and extensive deposition of immune complexes in the basement membrane of choroidal vessels and basement membranes of the RPE, which is facilitated from the high-volume choroidal flow [19, 23, 36, 37].

Systemic lupus erythematosus choroidopathy can be resolved in up to 82% of patients once systemic control of the disease is achieved [38]. Initial treatment is usually with immunosuppression. However, in some patients, corticosteroids may themselves induce central serous chorioretinopathy, in which case alternative agents should be