Fig. 18.11 (a) Bilateral periorbital and eyelid edema as an initial manifestation of systemic lupus erythematosus. (b) Complete resolution of bilateral periorbital and eyelid edema after high-dose systemic steroids

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

despite medical therapy with leflunomide, methotrexate, prednisone, rituximab, and intravenous and oral corticosteroids, but after monthly cyclophosphamide, the visual fields dramatically improved and the papilledema resolved.

Anterior Ocular Manifestations

The pathologic appearance of secondary Sjogren’s syndrome is a frequent finding in SLE. It may produce clinical ocular manifestations such as keratoconjunctivitis sicca and is strongly associated with the presence of HLA-DRW52 antigen and anti-Ro (SSA) and anti-La (SSB) antibodies [9, 12]. Corneal manifestations of SLE are confined primarily to ocular surface epitheliopathy secondary to keratoconjunctivitis sicca. Stromal keratitis is rare. Superficial punctate keratitis and recurrent epithelial erosions have been reported in patients with discoid lupus erythematosus.

Orbital inflammation in SLE may result in episodesofacuteproptosis,lidedema(Fig.18.11), conjunctival chemosis and hyperemia, and

limited ocular motility. Elevated intraocular pressure and myositis with enlargement of the extraocular muscles on CT scanning have also been reported. The eyelid may be involved in the cutaneous facial changes of lupus (Fig. 18.12). Discoid lesions of the eyelids can mimic chronic blepharitis.

Episcleritis or scleritis may also occur as a consequence of SLE, and scleritis is a reasonably accurate indicator of the presence of significant systemic activity in the SLE patient; scleritis will only resolve with adequate control of disease activity and usually does not respond to local therapy. Other, less common, ocular complications of lupus include conjunctivitis, keratitis, corneal staining, uveitis, and anterior segment neovascularization [17].

Drug-Related Ocular Manifestations

In addition to lupus-induced eye problems, the drugs used to treat the systemic disease have potential ocular side effects. Corticosteroids may

induce cataracts and glaucoma, and antimalarials can cause ocular toxicity including keratopathy, ciliary body involvement, lens opacities, and retinopathy. Chloroquine or hydroxychloroquine retinopathy is the major concern because others are more common but benign. The retinopathy of chloroquine or hydroxychloroquine may cause subtle, asymptomatic, reversible macular pigment mottling in its early phases and profound irreversible visual loss with a bull’s-eye pattern of pigmentary maculopathy in its later phases (Fig. 18.13a–d).

The incidence varies between studies and ranges from 0% to 4%, such variation being mainly due to the different definitions of retinopathy and use of different drug doses [56]. Early retinopathy is defined as an acquired paracentral scotoma on threshold visual field testing without any observable fundus changes. Advance chloroquine or hydroxychloroquine retinopathy is defined as an acquired paracentral scotoma on threshold visual field testing with associated parafoveal retinal pigment epithelial retinopathy. Although pathogenesis of retinopathy due to hydroxychloroquine is not well established, the similarity of its chemical structure to chloroquine and the characteristics of the retinopathy suggest that the mechanism may be analogous [56, 57]. Chloroquine is highly concentrated in the pigmented ocular tissues such as retinal pigment epithelium (RPE), binds to melanin, and remains

there for prolonged periods of time even after cessation of therapy [56, 58]. Histopathological studies of advance chloroquine retinopathy in humans revealed destruction of rods and cones with sparing of the foveal cones. This explains the fundoscopic appearance of the bull’s-eye maculopathy. It is suggested that the metabolism of the RPE is first affected, with disturbance of its function of phagocyting the physiologically shed outer segments of the photoreceptor cells [59, 60]. Animal studies have shown that the earliest reversible histopathological changes are membranous cytoplasmic bodies that accumulate in ganglion cells and degenerative changes in photoreceptor outer segments. Thus initially the drug may destroy ganglion cells and photoreceptors, with later involvement of the RPE [58].

Although the risk of developing maculopathy has been thought to depend on the total cumulative dose of the drugs, the size of the daily dose rather than the total dosage or duration of treatment may be the most important factor. Dosages of 400 mg/day or 6.5 mg/kg body weight/day of hydroxychloroquine, whichever is less, may permit very high intake without inducing clinical retinal toxicity. Chloroquine has a less clear safety profile and should be avoided where possible. Authors have stated that no patient should receive more than 250 mg/day of chloroquine. The dose of oral chloroquine 250 mg may be too small to achieve a rheumatologic therapeutic effect, but

Fig. 18.13 (a) Fluorescein angiogram (FA) shows a transmission defect corresponding to the area of central retinal pigment atrophy in a complete bull’s-eye lesion in a patient on chloroquine, who had lost central vision. (b) Left eye’s FA of same patient. (c) Spectral-domain

optical coherence tomography (SD-OCT) demonstrating an increase in choroidal reflectivity corresponding to the area of central retinal pigment atrophy in the same patient’s right eye. (d) Left eye’s OCT of same patient