Ocular manifestations of systemic lupus erythematosus: a clinical review

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2006 15: 3LupusV Peponis, V C Kyttaris, C Tyradellis, I Vergados and N M Sitaras

Ocular manifestations of systemic lupus erythematosus: a clinical review

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Ocular manifestations of systemic lupus erythematosus: a clinical review

V Peponis1,2, VC Kyttaris3*, C Tyradellis1, I Vergados4 and NM Sitaras2

1Department of Ophthalmology, General Hospital of Piraeus ‘Tzaneion’, Greece; 2Department of Pharmacology, Medical School,University of Athens, Greece; 3Department of Cellular Injury, Walter Reed Army Institute of Research, Silver Spring, MD, USA; and

42nd University Eye Clinic, Medical School, University of Athens, Greece

Although the eye itself is regarded an ‘immune-privileged’ organ, systemic lupus erythematosus(SLE) can affect every ocular structure, leading, if left untreated, to significant visual loss or evenblindness. Since ocular inflammation in SLE can antedate the diagnosis of the systemic disease andcause significant morbidity, prompt diagnosis and treatment of the underlying systemic autoimmunedisease is imperative. Lupus (2006) 15, 3–12.

Key words: antimalarials; keratoconjunctivitis sicca; retina; scleritis; systemic lupus erythematosus

Lupus (2006) 15, 3–12www.lupus-journal.com

REVIEW

Introduction

Systemic lupus erythematosus (SLE) is characterizedby a complex interplay between cellular and humoralfactors leading to a self-perpetuating autoimmuneresponse. The aberrantly activated immune system inSLE targets preferentially, but not exclusively, organssuch as the joints, skin, kidneys and brain.1

The eye, although not a primary target of immunemediated damage in SLE, can be affected in a varietyof ways resulting in significant ocular morbidity.Herein, we review recent reports on the ophthalmologicmanifestations of SLE, the effects of anti-inflammatorymedications on the eyes and treatment options for lupuseye disease.

Anterior segment manifestations

Anterior segment manifestations (Table 1) of SLE arerelatively common but not usually sight-threatening.The clinical picture is variable and depends on theocular structure involved. The most frequently encoun-tered symptoms are foreign body sensation, itching,

photophobia, heaviness of the eyelids, ‘red eye’, andsometimes decreased vision.

External ocular

The most common ocular manifestation of SLE iskeratoconjunctivitis sicca (KCS) presenting in approx-imately 25–35% of the patients.2–4 KCS is mainlycaused by a decrease in tear production leading toocular discomfort, irritation and burning sensation.Corneal involvement in KCS may manifest as punctateepithelial erosions, filamentary keratitis and in severecases KCS predisposes to bacterial keratitis and sterile ulceration5 that may even lead to perforation.

Secondary Sjögren’s syndrome, a disease character-ized by lymphocytic infiltration of the exocrine glands,may be the underlying cause of KCS in patients withsystemic autoimmune diseases such as SLE, and isstrongly associated with the presence of HLA-DRW52antigen and anti-Ro (SSA) and anti-La (SSB) antibod-ies.6 Although KCS is common in SLE, only five outof 60 (8.3%) patients7 with SLE fulfilled criteria forSjögren’s syndrome.

Eyelid

The periocular skin can be involved in lupus, espe-cially in discoid lupus erythematosus (DLE).8 Lower

© 2006 Edward Arnold (Publishers) Ltd 10.1191/0961203306lu2250rr

*Correspondence: Vasileios Kyttaris, Department of Cellular Injury,Walter Reed Army Institute of Research, 503 Robert Grant Avenue,Room 1N72, Silver Spring, MD 20910, USA. E-mail: [email protected] 18 July 2005; accepted 25 October 2005



eyelid involvement is seen in 6% of patients with DLEand may be associated with conjunctival injection andscarring.9 These lesions may initially be asymptomaticor confused for chronic blepharitis or eczema andtherefore remain undiagnosed for years.8,10–12

DLE presents usually with symmetrical erythemaand edema of the outer third of the lower eyelids.8,12

Involved areas have a tendency to heal with scarring,pigmentary changes, atrophy and loss of eyelashes(madarosis). Heliotropic discoloration, violaceousedema of the eyelids, eyelid tenderness or even persist-ent and severe periorbital edema are other oculocuta-neous presentations of both the systemic and discoidforms of lupus erythematosus.9,12–14

In unusual cases of DLE such as isolated eyelidinvolvement, a skin biopsy is needed to make the cor-rect diagnosis. The affected skin is characterized bylocalized hydropic degeneration of the basal cell layer(liquefaction degeneration)15 and band-like depositionof immunoglobulins at the dermal-epidermal junction(lupus band).13

Cornea

Corneal involvement in SLE is uncommon. Superficialpunctate keratopathy and corneal staining has beenreported with the incidence ranging from 6.5% to ashigh as 88% of the patients.16,17 Both KCS and theautoimmune process have been implicated in thepathogenesis of the epithelial keratopathy.16

In addition to producing KCS and corneal epithelialchanges, the inflammatory process in SLE can alsoaffect the perilimbal capillary arcades that nourish theperipheral cornea.18 This noninfectious peripheral

ulcerative keratitis (PUK) is frequently accompaniedby a necrotizing scleritis, as well as conjunctivaland episcleral involvement, and usually reflects thepresence of severe systemic vaso-occlusive disease.18

The incidence of corneal stromal and endothelialinvolvement in SLE is extremely low and can take theform of interstitial keratitis or corneal endothelitis(keratoendothelitis).19–22 They probably represent asterile inflammatory reaction associated with SLE.21

SLE and other connective tissue diseases are con-traindications for the performance of excimer laserablation of the cornea for the correction of refractiveerrors (photorefractive keratectomy (PRK) and laserassisted in situ keratosmileusis, (LASIK)). These autoim-mune conditions can modify the connective tissueresponse, resulting in an unpredictable reaction ofcorneal tissue to the laser ablation, and poor epithelialhealing; this in turn can trigger corneal haze andstromal melting. Therefore SLE, and in particularactive disease, is considered an absolute contraindica-tion for PRK and relative contraindication forLASIK.23–25

Conjunctiva

Conjunctival involvement, in the form of chronicconjunctivitis, is infrequent in SLE, although anincidence of 10% has been reported in one series.26

Severe cases with scarring and formation of adhesionsbetween palpebral and bulbar conjunctival (symble-pharon) have also been reported especially in case ofDLE conjunctivitis.13 Hypertrophic DLE occurring inthe conjunctiva and presented as papillomatous con-junctival mass, with accompanied chronic refractoryblepharoconjunctivitis, has been well described.27

In clinically normal bulbar conjunctival biopsyspecimens from patients with SLE, immunohisto-chemical evaluation demonstrates a 40–50% incidenceof deposition of immunoreactants in a linear patternalong the basement membrane.13,28

Sclera

Recurrent episodes of episcleritis have been reported,with its incidence found up to 28% of the cases.13 Thepatients present with redness, discomfort, tendernessand watering of the eyes and usually have a clinicallybenign course.

Scleritis is less common but it can cause severeocular morbidity. It can take the form of diffuse ante-rior or nodular scleritis.29 It has a tendency to recurwith increasing severity and frequency.30 Necrotizingscleritis is uncommon and usually occurs when the

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Table 1 Anterior segment manifestations

External ocularKeratoconjunctivitis sicca (KCS)Secondary Sjögren’s syndrome

AdnexalDiscoid lupus erythematosus (DLE) of the eyelidsPeriorbital edema, tenderness

Corneal involvementSuperficial punctate keratopathyRecurrent epithelial erosionsPeripheral ulcerative keratitis (PUK)Interstitial stromal keratitisCorneal endothelitis (keratoendothelitis)

Conjunctival involvementChronic conjunctivitisHypertrophic, papillomatous conjunctival lesions

Scleral involvementEpiscleritisScleritis (anterior-posterior, diffuse-nodular, necrotizing)

Uveal involvementUveitis (anterior-posterior, granulomatous-nongranulomatous)



renal and other systemic manifestations becomesignificant.30 Severe scleral inflammation can causestructural damage to the eye and can lead to scleralthinning, and in severe cases exposure of bare uvea oreven rupture of the globe after minor trauma.

Scleritis can be the presenting manifestation ofSLE so SLE must be considered in the differentialdiagnosis of patients with scleritis.31 Another importantfeature is that the activity of scleritis, and to a lesserdegree of episcleritis, closely parallel the systemicactivity of SLE.30

Uvea

SLE is a rare cause of anterior uveitis. SLE can also beassociated with posterior uveitis or uveitis secondaryto scleritis. In a large cohort of patients having uveitisless than 1% had a diagnosis of SLE.32 Another studyreported that the proportion of uveitis patients withSLE referred to a tertiary care center over a 10-yearperiod was 4.8% of all uveitis patients.33 Clinicalpresentation is variable, depending on the anatomiclocation, and is characterized by pain, photophobia,redness, especially circumcorneal (ciliary) injection,lacrimation, perception of floaters and impaired vision.

Tubulointerstitial nephritis and uveitis (TINU)syndrome is a rare immune-mediated disorder involv-ing both the kidney and the eye and sometimes isassociated with immune-related diseases, such asSLE.34 Ocular involvement in this disorder is typicallya bilateral, anterior, nongranulomatous uveitis.34

However, posterior segment involvement with granu-lomatous inflammation has also been reported.34

Posterior segment manifestations

The posterior segment manifestations (Table 2) of SLEhave important implications for visual function. Anypart of the posterior segment may be affected, includ-ing the retina, choroid and optic nerve. The retinalinvolvement is considered the second, after KCS, com-monest eye manifestation of lupus;35 visual impair-ment is usually secondary to macular involvement.

Retina

The classic finding in SLE retinopathy is the cotton-wool spot, an ischemic infract in the retinal nervefibre layer, which may be isolated or may be seen inassociation with areas of retinal edema, ischemia, hardexudates and hemorrhages.35 Although many of these

changes may be a part of the clinical picture of hyper-tensive retinopathy, as hypertension is often presentsecondary to lupus renal disease, lupus retinopathy canoccur as an independent manifestation of the underly-ing disease process in the absence of hypertension.16,36

Various abnormalities of the retinal vasculature, suchas vascular sheathing, arterial narrowing, capillary andvenous dilatation, tortuosity, microaneurysms andvenous engorgement have been described.37,38 Mostpatients with SLE retinopathy present with this type ofretinal vascular disease without evidence of vasculitis.The reported incidence of this more benign form ofSLE retinopathy varies between 3.3% and 28.1%, withthe incidence rising with the severity of systemic dis-ease in the population sampled.16,39 The patientsrespond well to systemic therapy and generally havegood visual prognosis.

SLE retinopathy is generally considered to be animmune complex mediated vasculopathy, based onprevious reports of immune complex deposition inretinal vessels in SLE.40 Rather than a true inflamma-tory vasculitis, the retinal vascular disease is thoughtto stem from fibrinoid degeneration with necrosis ofthe vessel walls.40 It is felt that atherosclerosis as aresult of hypertension, steroid use and dyslipidemia inSLE may have a role in the development of thisform of retinopathy.41 Fluorescein angiography of the

Ocular manifestations of lupusV Peponis et al.

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Table 2 Posterior segment manifestations

Retinal involvementCotton-wool spotsRetinal edema, ischemia, hard exudates, hemorrhagesRetinal vasculitisCentral retinal artery occlusion, cilioretinal artery occlusionRetinal vein occlusion (central or branch)Proliferative retinopathy, retinal neovascularizationPseudoretinitis pigmentosa-like retinopathy

Choroidal involvementMultifocal serous detachments of the retinal pigment epithelium (RPE)

and neural retinaChoroidal neovascularizationCentral serous chorioretinopathy (CSR)Ciliochoroidal effusions

Neuro-ophthalmological involvementOptic nerve involvement (papillitis, ischemic optic neuropathy,

retrobulbar optic neuritis)Ocular motor nerve palsiesVisual disturbances (amaurosis fugax, cortical blindness,

visual field defects)Pupillary abnormalities (light-near dissociation, Horner’s syndrome)Gaze abnormalities (internuclear ophthalmoplegia, one-and-a-half

syndrome)Nystagmus, ocular flutterPseudotumor cerebriMiller–Fisher syndrome

Other rare ophthalmic involvementsOrbital myositisOrbital pseudotumorOrbital apex syndromeBrown’s syndromeOcular ischemic syndrome



fundus in SLE patients, even in the absence of visualsymptoms and visible retinal abnormalities, hasdemonstrated fluorescein leakage, retinal capillarydilatation and microaneurysms in patients with mildto moderate disease activity.36 Several studies reportthat retinal vascular disease in SLE patients parallel thesystemic disease activity,16,42 and that the effectivetreatment of the systemic disease, along with simulta-neous control of any associated systemic hyperten-sion, results also in concurrent decrease in the retinallesions, especially the disappearance of cotton woolspots.16,43

In contrary, severe occlusive retinopathy or vasculi-tis is a rare form of retinopathy in SLE often affectingsmaller retinal arteries and arterioles. Unlike themilder, more benign forms of retinopathy, visual lossoften ensues.44 The histopathological findings includeperivascular lymphocytic infiltrates, endothelialswelling and thrombus formation, with occlusion ofretinal and choroidal vessels, including the choriocap-illaries.45 Interestingly, the severe form of vaso-occlusive retinopathy is associated with similarchanges in the central nervous system (CNS) vascula-ture.39,44,46,47 Retinopathy in SLE is a marker ofpoor prognosis for survival, that is SLE patientswith retinopathy have overall worse prognosis anddecreased survival, compared to SLE patients withoutretinopathy.39

Antiphospholipid antibodies and microthrombosismay also have a role in the pathogenesis of this condi-tion and this vaso-occlusive phenomenon may be partof the antiphospholipid syndrome.41,48,49 Theseautoantibodies are thrombogenic50 and they areassociated with both CNS and ocular vaso-occlusivephenomena50,51 that can manifest as visual disturbances,transient monocular blindness and chorioretinopathy inpatients with SLE.52 A higher incidence of antiphospho-lipid antibodies in SLE patients with retinal vasculardisease, compared to those without (77% versus 29%),has been reported.53 However, only 21–65% of thepatients with SLE are reported to have lupus anticoagu-lants and related antiphospholipid antibodies.54

A consequence of the diffuse arteriolar occlusionand capillary nonperfusion encountered in patientswith severe retinal vaso-occlusive disease or vasculitisis that some of these patients develop proliferativeretinopathy and retinal neovascularization; this in turnmay lead to vitreous hemorrhage and tractional retinaldetachment necessitating surgical intervention.47 Ingeneral this vaso-occlusive process is irreversible andtreatment is aimed at preventing complications arisingfrom neovascularization. Close monitoring of thesepatients with routine fundoscopic exams and fluores-cein angiography if necessary, is mandatory even inthe absence of systemic flare-up.

In addition to microangiopathy described above,SLE has been linked with occlusions of larger diame-ter retinal vessels such as the central retinal artery, thecilioretinal artery and retinal vein (central or branch),which present with usually severe visual loss andguarded prognosis.38,46,47,55

Rare retinal manifestations reported in patients withSLE include exudative macular edema associated withfrosted branch periphlebitis56 and a pseudoretinitispigmentosa-like picture with bilateral retinal pigmentepithelium (RPE) changes.57

Choroid

Although choroidopathy is less common thanretinopathy in SLE is a well recognized manifestationof the disease.54,58–60 It is usually seen in severely illor hypertensive patients. It is typically manifest asmultifocal serous detachments of the RPE and neuralretina, with the transudation of the accumulated fluidthrough Bruch’s membrane and RPE affected by thechoroidal ischemia and inflammation. The presentingsymptom is visual loss, which depends on theextent of macular involvement.35,58 The detachmentsmay regress with improved control of the systemicdisease.59

Several mechanisms of serous detachment in SLEchoroidopathy can be considered: 1) choroidal vascu-lopathy, causing ischemia-induced RPE dysfunction,2) choroidal inflammation-induced RPE dysfunction,3) corticosteroid-induced RPE dysfunction.58,59,61–63

The dysfunction of the choroidal vasculature in SLEand the accompanied RPE defects could sometimeslead to choroidal neovascularization.64 Increasedchoroidal permeability, leading to ciliochoroidal effu-sions with resultant angle closure glaucoma, hasbeen described as an uncommon complication of SLEchoroidopathy.60,65 Central serous chorioretinopathy(CSR) has also been associated as a complicating eventin SLE, although it is uncommon.66

Fluorescein angiography in cases of lupuschoroidopathy demonstrates multiple sites of leakagefrom the choroid into the sub-RPE and subretinalspaces.67 In lupus patients, indocyanine green angiog-raphy (ICG) may reveal congested and dilatedchoroidal vessels. In some cases the ICG dye stainsthe walls of the choroidal vessels, suggesting thepresence of a choroidal vascular inflammatorycomponent.68 Histopathological findings in SLEchoroidopathy are massive mononuclear infiltration,diffuse thickening of medium-sized choroidal vesselsand extensive deposition of immune complexes,which is facilitated from the high volume choroidalflow.40,69,70


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Neuro-ophthalmological manifestations

The incidence of neuro-ophthalmological manifesta-tions ranges from 3% to 30% in various studies.71,72

The clinical presentation is highly variable but gener-ally the visual outcome is poor.

The most common manifestation is that of opticnerve damage. Depending on the exact anatomical areaof the lesion, optic nerve damage presents as papillitis,ischemic optic neuropathy (anterior or posterior) orretrobulbar optic neuritis.73–76 The optic nerve damageis believed to be secondary to an occlusive vasculitis ofthe small arterioles of the nerve, which leads todemyelination and/or axonal necrosis.75,77 Signs ofoptic nerve disease include reduced visual acuity,impairment of colour vision (dyschromatopsia),diminished light brightness sensitivity, decreased con-trast sensitivity, afferent pupillary defect and visualfield defects. Fundoscopy discloses a swollen discexcept in the case of retrobulbar neuritis that is charac-terized by a normal appearing optic disc; optic atrophy,also seen in fundoscopy, represents the end result ofoptic nerve involvement.

Lesions of the posterior visual pathways and retrochi-asmal lesions are relatively uncommon, but can lead tosevere disability.78 These include pupillary abnormali-ties, such as light-near dissociation or Horner’s syn-drome, visual disturbances ranging from transientamaurosis fugax to cortical blindness, visual hallucina-tions, as well as visual field defects and scotomas.77,79,80

These subtle complications suggest vasculopathy of theposterior cerebral circulation, resulting in an occipitalinfract.78,81 An interesting association between lupusanticoagulants and neuro-ophthalmological manifesta-tions has also been reported.82–85

Neuro-ophthalmological manifestations secondaryto lesions of the ocular motor system include gazeabnormalities, such as internuclear ophthalmoplegia(INO),86 the one-and-a-half syndrome,87 as well asocular motor nerve palsies.88,89 The incidence ofcranial neuropathy is reported to range from 5% to42% and is often associated with multiple cranialnerves involvement.88,89 Pseudotumor cerebri or idio-pathic intracranial hypertension has been described inpatients with SLE.90 Manifestations consistent withMiller–Fisher syndrome (ataxia, areflexia, ophthalmo-plegia) in SLE has also been reported.91

The neuro-opthalmological manifestations of SLEalso include Devic’s syndrome (neuromyelitis optica)that is characterized by optic neuropathy and spinalmyelitis. It can present as an isolated disease or in thecontext of multiple sclerosis or SLE. Inflammationand/or thrombosis of medium to small vessels in thecentral nervous system are thought to underlie thenerve damage in this syndrome. The most common

clinical presentation of Devic’s syndrome is that ofblindness and paraplegia that are oftentimes refractoryto treatment.92,93

Other rare ophthalmic manifestations

Orbital involvement is SLE has been reported.94–97

It can take the form of orbital inflammation withmarkedly enlarged extraocular muscles (inflammatorymyositis), pain and proptosis. Sometimes it can havethe clinical picture of orbital pseudotumour, withdiffuse orbital inflammation and no discrete lesion, orthe development of an orbital mass effect.95,98

Whitefield et al. described a patient with SLEand concomitant development of Brown’s syndromecausing vertical diplopia.99 A transient tenosynovitisaffecting the superior oblique tendon may be theprobable underlying pathological mechanism.100

Drug-related manifestations

In addition to lupus-induced eye problems, the drugsused to treat the systemic disease have potential ocularside effects. Both steroids and antimalarials, the twomain classes of drugs used for the treatment of SLE,have ocular side effects.

Ocular complications of corticosteroids have beenwell documented, including among others, posteriorsubcapsular cataract (PSC), elevated intraocular pres-sure, steroid-induced glaucoma, secondary infectionswith bacteria and fungi, recurrences of herpes simplexkeratitis, CSR, and delayed corneal and scleral woundhealing.100 Side effects have been reported secondaryto intravenous, oral, topical (ocular and cutaneous),intranasal, inhaled, and injected (epidural, subconjunc-tival, sub-Tenon, and periocular) corticosteroids.101

The incidence of PSC associated with steroid useincreases with increased dosage and duration of treat-ment, but there is considerable inter-individual varia-tion in susceptibility.102 Although PSC have beenreported to develop after as little as 5 mg/day of oralprednisone for as short as two months, the usual timeuntil onset is at least one year with dosage equivalentto 10 mg/day of oral prednisone.103,104 The incidenceof corticosteroid-induced cataract reported in anumber of randomized, controlled trials ranged from6.4% to 38.7% after oral corticosteroid use.105,106

Antimalarials (chloroquine, hydroxychloroquine)can deposit in ocular tissues causing toxicity. Cornealepithelial deposits (vortex keratopathy, verticillata) canbe demonstrated in most patients taking chloroquine,often developing within two to three weeks of initiation,but these changes very rarely impair vision.107,108,109


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Corneal deposition of chloroquine occurs in up to 90%of patients receiving 250 mg/day of chloroquine;however, patients receiving 400 mg/day of hydroxy-chloroquine almost never show changes in thecornea.107,109 If corneal changes are present withhydroxychloroquine, often the drug has been overdosedand may associated with a greater risk of retinopathy.110

Antimalarials can infrequently affect ciliary body(accommodative weakness with difficulty in reading)and lens (PSC).111,112

By contrast, retinopathy caused from antimalarialsis a severe ocular side effect presenting with bilateral,reproducible, and permanent visual field abnormali-ties.113 Early retinal changes consist of a pigmentarystippling or granular appearance of the macula, withthe patient still being asymptomatic. Advancedretinopathy may show the typical ‘bull’s eye’ macu-lopathy, associated with impaired visual acuity andcentral visual field defects.112 These changes ofadvanced maculopathy are irreversible and mayprogress even after cessation of the drug.115 Althoughthe risk of developing maculopathy has been thoughtto depend on the total cumulative dose of the drug,the daily dose rather than the total dosage or durationof treatment may be the most important factor.107

Retinal toxicity for chloroquine appears to occureven with daily doses as low as 250 mg, comparedto 400 mg of hydroxychloroquine.107 Calculation ofideal body weight in the dosing of antimalarial isimportant to reduce the risk of retinopathy, especiallyin obese patients. The risk is 7.4% for chloroquine ifthe daily dosage is kept below 3 mg/kg of ideal bodyweight,107 and as long as the daily maintenance doseof hydroxychloroquine is kept at or below 6.5 mg/kgof ideal body weight the risk of retinal toxicity isminimal, much less than 1%.116,117

The recent recommendations of the AmericanAcademy of Ophthalmology adopt screening strategiesfor antimalarial toxicity after a baseline examination,because of the anticipated risk to the patient.118 Theproposed routine screening includes an ophthalmo-logic examination and visual field testing by an Amslergrid or static automated macular perimetry. Optionaltests include colour testing, fundus photography,fluorescein angiography, and multifocal electroretino-graph (ERG).118,119 The patient should be assessed sixmonths after starting antimalarial drugs, and as long asthe dosage of hydroxychloroquine is kept at 400 mg/dayor less, annual examination is often adequate.

Treatment

Since the ocular complications of SLE are generallyassociated with active disease elsewhere in the body,

control of the systemic disease may lead to resolutionof ocular manifestations.

Nonsteroidal anti-inflammatory agents or antimalar-ial therapy (especially hydroxychloroquine sulphate)may be sufficient in relatively mild ocular disease(episcleritis, DLE). Antimalarials however cannot treatsuccessfully the vasculitic component of SLE.

The presence of severe manifestations of SLE suchas scleral, retinal, choroidal, neuro-opthalmological ororbital involvement requires systemic therapy withsteroids.59,75,120–122 Initial empiric treatment with corti-costeroids is typically oral (prednisone, 1 mg/kg/day),with or without initial pulse with intravenous corticos-teroids (methylprednisolone 1 g/day for three days).Higher daily dosages of up to 2 mg/kg/day of oralprednisone have been used in patients with retinalvasculitis.122 In some cases, especially of asymmetri-cal ocular involvement, systemic corticosteroid may besupplemented with regional corticosteroid injection(triamcinolone acetonide, 40 mg/mL, in sub-Tenon orperibulbar injections). Doses and/or durations of treat-ment depend on the clinical severity and initialresponse.122,123 Regardless of the treatment scheduleused, many patients will not exhibit clinical improve-ment until three to four weeks following initiation oftherapy.

Despite the high success rate with corticosteroids,some cases of severe ocular disease may be unrespon-sive or inadequately controlled by these drugs.124

When corticosteroid therapy fails to control thedisease or when therapy is expected to be requiredfor longer than three months, institution of immuno-suppressive agents such as cyclophosphamide, aza-thioprine, methotrexate, cyclosporine, chlorambucil,mycophenolate mofetil, and tacrolimus may benecessary.124–126

Antiplatelet treatment (aspirin) and anticoagulation(warfarin), in combination with immunosuppressionmay have a role in limiting the progression of the vaso-occlusive retinopathy and in the secondary preventionof thrombosis in the presence of antiphospholipid antibodies.43,127

Laser panretinal photocoagulation (PRP) and vitre-oretinal surgical procedures may be necessary to treatcomplications associated with retinal vasculitis; theseinclude persistent neovascularization with nonclearingor recurrent vitreous hemorrhage, tractional retinaldetachment and neovascular glaucoma.122,123 In partic-ular, PRP results in clinical benefit in up to 54% ofpatients.43

Adjunctive therapy for KCS such as tear supple-ment, punctal occlusion, eyelid hygiene and topicalcyclosporin is crucial.37 Topical cyclosporine 0.05% isa safe, well-tolerated and effective new medication,which reduces cell-mediated inflammation of lacrimal


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tissue.128 Oral cholinergic agents such as pilocarpineand cevimeline are quite effective in relieving thesymptoms associated with KCS and secondarySjögren’s syndrome.129

Treatment of DLE is dependent upon the severity ofskin involvement and the presence of associatedsystemic disease. In some cases, prescribed treatmentsfor systemic disease will alleviate associated cuta-neous symptoms.12,15 Direct intralesional infiltrationwith corticosteroid suspension has been reported torapidly improve eyelid lesions in lupus erythematosusand such treatment may be necessary in the hyper-trophic forms of discoid lupus.130 Patients should beadvised that atrophic changes in the lid may be associ-ated with corticosteroid injection, as well as with thenormal course of resolution of discoid skin lesions.130

Treatment of isolated refractory lid lesions withsystemic hydroxychloroquine at a dose of 200 mg/dayfor a three-month period has also been reported.12,35

A surgical approach to revision of eyelid changesassociated with lupus erythematosus should bedeferred until medical control of the condition hasbeen established, particularly since recurrent diseasehas been reported to occur at previous surgical incisionsites.12

Episcleritis has a benign course without seriousocular morbidity and therapy with nonsteroidal agentsmay be tried.37 Although PUK in the setting of SLEis rare, it signifies advanced disease that requiressystemic corticosteroids, and, possibly, cytotoxictherapy.131 Surgical management of PUK is reservedfor some cases in order to preserve the integrity ofthe globe. Options include penetrating keratoplasty,

lamellar grafts, amniotic membrane transplantationand use of tissue adhesive.132 Despite improvement ofgraft survival with cytotoxic therapy, the outcomes ofpenetrating keratoplasty are disappointing.

Conclusion

SLE is a chronic autoimmune disease with variableclinical course, both in terms of rate of progression andseverity. Ophthalmic manifestations in patients withSLE can be highly variable and can lead to blindness.(severe ocular manifestations of SLE summarized inTable 3). Minimizing ocular morbidity with preserva-tion of vision can be challenging and is accomplishedby close monitoring of the patient from both the oph-thalmologist and the rheumatologist. Furthermore,ocular lupus can precede the onset or reactivation ofthe systemic disease by several months. Therefore allpatients diagnosed with ocular lupus, even in theabsence of systemic symptoms and signs, should becarefully evaluated by a rheumatologist for potentiallytreatable and preventable complications of the disease.Although new diagnostic and therapeutic tools forocular lupus are available, much remains to be learnedregarding the pathophysiology and the correcttherapeutic approaches for the ocular manifestationsof SLE.

Acknowledgement

We would like to thank Dr George C Tsokos for criti-cally reviewing this manuscript.


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Table 3 Vision-threatening ocular manifestations in SLE

Peripheral ulcerative keratitis Scleritis Occlusive retinopathy Optic neuropathy

Clinical Photophobia, foreign Pain, tearing Monocular blindness, Reduced visual acuity,presentation body sensation, visual disturbances dyschromatopsia, diminished

tearing, reduced light brightness sensitivity,visual acuity decreased contrast sensitivity,

afferent pupillary defect,visual field defects

Disease Concomitant scleritis Mainly found in severe Found in patients with Cerebral vasculopathy may be association may be present forms of SLE but antiphospholipid syndrome; present

occasionally can exist also in severe hypertension. before the diagnosis of Due to vasculopathy rather systemic lupus than vasculitis

Outcome Loss of vision corneal May result in sclera thining Leads to retinal infarcts and Optic nerve atrophyperforation and exposure of uvea neovascularization

(proliferative retinopathy)Treatment Control of systemic disease High dose corticosteroids/ Anticoagulation treatment of High dose corticosteroids

with corticosteroids/ cytotoxics underlying disease and control cytotoxics of hypertension.

May need surgical PRP, vitreo-retinal procedureintervention



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Ocular manifestations of systemic lupus erythematosus: a clinical review