Ophthalmology – Systemic Lupus Erythematosus

What the Disease Represents

Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disease characterized by:

• Autoantibody production
• Immune-complex formation
• Complement activation
• Inflammation and vascular injury

The disease typically follows a:

Relapsing-remitting course

and may affect:

• Skin
• Joints
• Kidneys
• Hematologic system
• Nervous system
• Cardiovascular system
• Eyes

Ocular manifestations may sometimes reflect:

Active or severe systemic lupus.

Why SLE Matters to Ophthalmologists

Almost any ocular structure can be affected.

Important manifestations include:

• Keratoconjunctivitis sicca
• Eyelid discoid lupus lesions
• Episcleritis
• Scleritis
• Peripheral ulcerative keratitis
• Uveitis
• Retinal microangiopathy
• Severe vaso-occlusive retinopathy
• Choroidopathy
• Optic neuropathy
• Cranial neuropathies
• Hydroxychloroquine retinal toxicity

Among these, severe retinal vascular disease and optic nerve involvement are particularly important because they can cause:

Permanent visual loss.

Who Is Most Commonly Affected

SLE occurs predominantly in:

Women of reproductive age

with a female predominance of approximately:

9:1

Disease severity and prevalence vary among populations and are influenced by:

• Genetic susceptibility
• Hormonal factors
• Environmental triggers
• Socioeconomic and healthcare factors

How Autoimmunity Develops

SLE results from loss of tolerance to self-antigens.

Important mechanisms include:

• Abnormal clearance of apoptotic material
• B-cell activation
• Autoantibody production
• Immune-complex deposition
• Complement activation
• Type I interferon signaling
• T-cell dysregulation

Vascular injury may result from:

• Immune-complex vasculopathy
• Endothelial dysfunction
• Thrombosis

Genetic Susceptibility

SLE is polygenic rather than caused by a single gene.

Associations involve:

• HLA loci
• Complement pathways
• Interferon signaling
• B-cell regulation

Family members have increased risk, but inheritance is:

Not Mendelian.

Common Systemic Manifestations

Patients may have:

• Malar rash
• Photosensitivity
• Arthritis
• Oral ulcers
• Serositis
• Nephritis
• Cytopenias
• Neurologic disease
• Constitutional symptoms

Fatigue is particularly common.

Modern Classification Framework

Older teaching used the rule:

4 of 11 ACR criteria

This has largely been replaced for classification purposes by the:

2019 EULAR/ACR criteria

These require:

1. Positive ANA at least once as an entry criterion
2. Weighted clinical and immunologic features
3. A cumulative score of ≥10 points

Classification criteria support research and standardized case definition but do not replace:

Clinical diagnosis by the treating physician.

Important Lupus Autoantibodies

Common serologic markers include:

• ANA – highly sensitive but nonspecific
• Anti-dsDNA – relatively specific and often associated with nephritis/activity
• Anti-Sm – highly specific
• Anti-Ro/SSA
• Anti-La/SSB
• Antiphospholipid antibodies

Complement levels such as:

• C3
• C4

may fall during active disease.

Antiphospholipid Antibody Syndrome

SLE may coexist with:

Antiphospholipid syndrome (APS)

Relevant antibodies include:

• Lupus anticoagulant
• Anticardiolipin antibody
• Anti-β2-glycoprotein I antibody

APS increases risk of:

• Arterial thrombosis
• Venous thrombosis
• Retinal artery occlusion
• Retinal vein occlusion
• Cerebral ischemia

This is particularly important in patients with:

Severe vaso-occlusive retinal disease.

Common Eye Symptoms

Patients may report:

• Dryness
• Burning
• Foreign-body sensation
• Redness
• Photophobia
• Ocular pain
• Floaters
• Diplopia
• Blurred vision
• Sudden visual loss

Symptoms depend heavily on the structure involved.

Eyelid Manifestations

Discoid lupus erythematosus may affect the eyelids.

Findings can include:

• Scaly plaques
• Erythema
• Atrophy
• Dyspigmentation
• Madarosis
• Lid-margin distortion

It may resemble:

• Chronic blepharitis
• Seborrheic disease

Ocular Surface Disease

The most frequent ophthalmic problem is:

Dry eye disease

often related to:

• Lacrimal gland dysfunction
• Secondary Sjögren disease
• Meibomian gland dysfunction
• Medication effects

Corneal Findings

Dry eye may produce:

• Reduced tear meniscus
• Punctate epithelial keratitis
• Filamentary keratitis
• Fluctuating vision

Less commonly SLE may cause:

• Interstitial keratitis
• Peripheral ulcerative keratitis
• Corneal thinning

Peripheral Ulcerative Keratitis

PUK is an uncommon but potentially serious manifestation.

It may occur with:

• Scleritis
• Active systemic vasculitis

Findings include:

• Peripheral epithelial defect
• Stromal thinning
• Inflammatory infiltrate

This should prompt:

Urgent systemic evaluation and immunosuppressive treatment.

Episcleritis

Episcleritis generally causes:

• Sectoral superficial redness
• Mild discomfort
• Normal vision

Superficial episcleral vessels typically:

Blanch with phenylephrine.

It is usually less threatening than scleritis.

Scleritis

Scleritis may present with:

• Deep boring pain
• Violaceous redness
• Globe tenderness
• Possible visual decline

Deep vessels generally:

Do not blanch substantially with phenylephrine.

Scleritis in an SLE patient can indicate:

Significant systemic inflammatory activity.

Anterior Uveitis

Anterior uveitis is less common than ocular surface or retinal disease.

Possible findings include:

• Cells
• Flare
• Posterior synechiae

Severe hypopyon uveitis is unusual and should prompt consideration of:

• Infection
• Behçet disease
• Other inflammatory disorders

Lupus Retinopathy

The classic retinal manifestation is:

Lupus retinal microangiopathy

which reflects systemic vascular injury.

Common findings include:

• Cotton-wool spots
• Intraretinal hemorrhages
• Microaneurysms
• Hard exudates
• Vascular tortuosity

Cotton-wool spots represent:

Focal retinal nerve fiber layer ischemia.

Why Lupus Retinopathy Matters

Retinopathy often correlates with:

• Active systemic disease
• Renal disease
• CNS involvement
• Hypertension

Therefore retinal findings may serve as a marker of:

More severe systemic lupus activity.

Severe Vaso-Occlusive Retinopathy

A much more serious phenotype is:

Occlusive lupus retinal vasculopathy

which can produce:

• Extensive capillary nonperfusion
• Branch retinal artery occlusion
• Central retinal artery occlusion
• Branch retinal vein occlusion
• Central retinal vein occlusion
• Combined arterial and venous occlusion

Role of Antiphospholipid Antibodies

Severe thrombotic retinal vascular disease should raise suspicion for:

Antiphospholipid syndrome

especially when occlusion is:

• Extensive
• Bilateral
• Recurrent
• Occurring at a young age

Ischemic Retinal Complications

Extensive nonperfusion can lead to:

• Retinal neovascularization
• Neovascularization of the disc
• Vitreous hemorrhage
• Fibrovascular proliferation
• Tractional retinal detachment
• Neovascular glaucoma

These complications may threaten vision even after systemic inflammation is controlled.

Fluorescein Angiography

FA is particularly useful when retinal vascular disease is suspected.

It can demonstrate:

• Capillary nonperfusion
• Vascular leakage
• Retinal vasculitis
• Macular ischemia
• Neovascularization

Wide-field angiography can help quantify:

Peripheral retinal ischemia.

OCT

Macular OCT is useful for detecting:

• Macular edema
• Intraretinal fluid
• Subretinal fluid
• Ischemic retinal thinning
• Hydroxychloroquine toxicity

OCT is also important for following:

Structural response to treatment.

OCT Angiography

OCTA may demonstrate:

• Reduced capillary density
• Deep and superficial plexus abnormalities
• Foveal avascular zone enlargement

It can complement FA but cannot directly demonstrate:

Vascular leakage.

Lupus Choroidopathy

SLE may rarely produce:

Choroidal vascular dysfunction

with:

• Serous retinal detachment
• RPE detachments
• Choroidal ischemia
• RPE changes

It is often associated with:

• Severe systemic hypertension
• Lupus nephritis
• Active systemic disease

Why Choroidopathy Can Develop

Possible mechanisms include:

• Choroidal vasculitis
• Immune-complex deposition
• Choroidal ischemia
• Severe hypertension
• RPE dysfunction

These impair normal removal of:

Subretinal fluid.

Distinguishing Lupus Choroidopathy From CSC

This distinction can be challenging because SLE patients may receive corticosteroids, which can precipitate:

Central serous chorioretinopathy

Thus subretinal fluid in an SLE patient may reflect:

• Active lupus choroidopathy
• Steroid-associated CSC
• Hypertensive choroidopathy

The management differs substantially.

Optic Nerve Disease

Optic nerve involvement is uncommon but potentially severe.

Manifestations include:

• Optic neuritis
• Ischemic optic neuropathy
• Optic disc edema
• Optic nerve vasculitis
• Papilledema from raised intracranial pressure

Lupus Optic Neuropathy

Patients may develop:

• Sudden or subacute visual loss
• Dyschromatopsia
• RAPD
• Visual-field defects

Mechanisms may include:

• Inflammation
• Small-vessel ischemia
• Thrombosis

Severe optic neuropathy generally requires:

Urgent systemic treatment.

Neuro-Ophthalmic Manifestations

CNS lupus or associated vascular disease may cause:

• Cranial nerve palsies
• Internuclear ophthalmoplegia
• Homonymous visual-field defects
• Cortical visual loss
• Nystagmus
• Ocular motor abnormalities

When Neuroimaging Is Needed

MRI brain/orbits ± vascular imaging should be considered with:

• Optic neuropathy
• Cranial neuropathy
• Homonymous field loss
• Focal neurologic symptoms
• Suspected CNS vasculitis or thrombosis

Infection Must Always Be Considered

SLE patients are often receiving:

• Corticosteroids
• Antimetabolites
• Biologic agents
• Other immunosuppressive drugs

New ocular inflammation may therefore actually represent:

Infection rather than autoimmune flare.

Important infections include:

• HSV
• VZV
• CMV
• Toxoplasmosis
• Tuberculosis
• Syphilis

Escalating immunosuppression without considering infection can be dangerous.

Dry Eye Treatment

Ocular surface disease may be treated with:

• Preservative-free artificial tears
• Lubricating gel or ointment
• Treatment of meibomian gland dysfunction
• Topical cyclosporine
• Lifitegrast or another approved anti-inflammatory dry-eye therapy

Severe disease may require:

• Serum tears
• Punctal occlusion
• Scleral lenses

Treating Episcleritis

Mild disease may respond to:

• Lubrication
• Oral NSAIDs when necessary

Frequent recurrence should prompt assessment of:

Systemic disease activity.

Treating Scleritis and PUK

These usually require:

Systemic anti-inflammatory/immunosuppressive therapy

rather than topical drops alone.

Treatment may include:

• Systemic corticosteroids
• Steroid-sparing immunomodulators
• Biologic therapy according to systemic disease

Treating Lupus Retinal Vasculitis

Sight-threatening retinal inflammation generally requires:

Rapid systemic control of lupus activity

often using:

• High-dose systemic corticosteroids
• Additional immunosuppression

depending on severity.

Agents may include:

• Mycophenolate
• Cyclophosphamide
• Azathioprine
• Rituximab
• Other disease-directed therapies

Management should be coordinated with:

Rheumatology.

Managing Vaso-Occlusive Disease

If APS or another thrombotic mechanism is present, treatment may require:

Antithrombotic therapy

under systemic specialist supervision.

This may include:

• Anticoagulation
• Selected antiplatelet therapy

Anticoagulation should not be prescribed solely because an SLE patient has retinopathy; it is used when there is an established:

Thrombotic/APS indication.

Managing Retinal Ischemia

Extensive retinal nonperfusion with neovascularization may require:

Panretinal photocoagulation

Anti-VEGF therapy can be useful as an adjunct for:

• Neovascularization
• Macular edema

but it does not replace treatment of the underlying systemic disease.

Vitrectomy

Pars plana vitrectomy may be required for:

• Nonclearing vitreous hemorrhage
• Tractional retinal detachment
• Complex proliferative disease

Treating Lupus Choroidopathy

Treatment centers on correcting the underlying systemic problem:

• Control severe hypertension
• Treat active lupus nephritis
• Suppress systemic inflammation when appropriate

Serous detachments often improve as systemic disease comes under control.

Hydroxychloroquine in SLE

Hydroxychloroquine (HCQ) is a cornerstone systemic therapy for many patients with SLE because it reduces:

• Disease flares
• Thrombotic risk in selected populations
• Long-term organ damage

unless contraindicated.

Its major ophthalmic concern is:

Retinal toxicity.

Hydroxychloroquine Toxicity

HCQ toxicity primarily affects:

• Photoreceptors
• RPE

Typical advanced disease produces:

Bull’s-eye maculopathy

but modern screening aims to detect toxicity well before this appears clinically.

Safe Hydroxychloroquine Dosing

A major modern correction is that dosing should generally be kept at:

≤5 mg/kg/day using actual body weight

rather than the older threshold of 6.5 mg/kg based on ideal body weight.

Major Risk Factors for HCQ Retinopathy

Risk increases with:

• Higher daily dose
• Longer treatment duration
• Renal impairment
• Concurrent tamoxifen use

Pre-existing macular disease may complicate screening interpretation.

Modern HCQ Screening

Patients should have a:

Baseline ophthalmic examination

soon after starting therapy to document pre-existing macular disease and establish an imaging reference.

For patients at standard risk, annual screening generally begins after:

5 years of treatment.

Earlier annual screening is appropriate when major risk factors are present.

Core Hydroxychloroquine Screening Tests

Modern screening relies primarily on:

• Spectral-domain OCT
• Automated visual field testing

Common field strategy:

• 10-2 in many non-Asian patients

Because toxicity may be more pericentral in many Asian patients:

• Wider fields such as 24-2C, 24-2, or 30-2
• Wider OCT assessment

may be appropriate.

Additional HCQ Tests

Useful confirmatory tests include:

• Fundus autofluorescence
• Multifocal ERG

Amsler grid and color vision testing are:

Not sufficiently sensitive as primary screening tests.

Why Early HCQ Detection Is Critical

Hydroxychloroquine toxicity can continue to progress after the drug is stopped because of persistent retinal drug effects.

Therefore:

Established toxicity is irreversible.

The goal of screening is detection before meaningful central visual loss occurs.

Corneal Verticillata From Antimalarials

Antimalarial therapy may also cause:

Corneal verticillata

These whorl-like epithelial deposits are usually:

• Asymptomatic
• Reversible
• Not predictive of retinal toxicity

They generally do not require treatment.

Corticosteroid-Related Eye Problems

Patients treated chronically with systemic or topical steroids are at increased risk of:

• Posterior subcapsular cataract
• Ocular hypertension
• Steroid-induced glaucoma

These complications should be monitored during prolonged therapy.

Multidisciplinary Management

Serious ocular lupus manifestations often require collaboration among:

• Ophthalmology
• Rheumatology
• Nephrology
• Neurology
• Hematology

depending on the systemic phenotype.

Follow-Up Approach

Follow-up is individualized according to:

• Ocular manifestation
• Systemic activity
• Treatment
• Medication toxicity

Monitor as appropriate:

• Visual acuity
• IOP
• Ocular surface
• Optic nerve
• OCT
• Visual fields
• Retinal vascular status

Expected Visual Outcome

Most patients with uncomplicated dry eye or episcleritis maintain:

Excellent visual prognosis.

Visual prognosis becomes more guarded with:

• Severe vaso-occlusive retinopathy
• Macular ischemia
• Optic neuropathy
• Extensive choroidopathy
• Delayed treatment

Features Linked to Poorer Vision

Particularly concerning findings include:

• Extensive retinal capillary nonperfusion
• Macular ischemia
• Central retinal artery occlusion
• Neovascularization
• Optic nerve ischemia
• Recurrent severe inflammatory disease

Long-Term Eye Complications

Potential complications include:

• Chronic dry eye
• Corneal ulceration
• Scleritis
• Cataract
• Glaucoma
• Retinal vascular occlusion
• Vitreous hemorrhage
• Tractional retinal detachment
• Neovascular glaucoma
• Macular ischemia
• Optic neuropathy
• Permanent visual loss

High-Yield Takeaways

• SLE is a multisystem autoimmune disease capable of affecting essentially every ocular structure.
• The most common ophthalmic manifestation is usually ocular surface disease/dry eye, often associated with Sjögren disease.
• Lupus retinopathy classically produces cotton-wool spots, hemorrhages, microaneurysms, and vascular abnormalities.
• Retinal vascular disease may parallel active systemic or CNS lupus and can therefore be an important marker of disease severity.
• Severe vaso-occlusive retinopathy can produce extensive capillary nonperfusion, artery or vein occlusion, retinal neovascularization, vitreous hemorrhage, and tractional retinal detachment.
• Severe retinal thrombosis should raise suspicion for antiphospholipid syndrome.
• Anticoagulation is used for an appropriate APS/thrombotic indication, not automatically for all lupus retinopathy.
• Lupus choroidopathy may produce serous retinal detachment and is often associated with severe hypertension or lupus nephritis.
• In an SLE patient on corticosteroids, subretinal fluid may alternatively represent steroid-associated central serous chorioretinopathy.
• Scleritis and peripheral ulcerative keratitis generally require systemic treatment and may indicate severe autoimmune activity.
• Optic neuropathy is uncommon but potentially devastating and requires urgent systemic evaluation.
• In immunosuppressed SLE patients, always consider infection before labeling new ocular inflammation as a lupus flare.
• Hydroxychloroquine is an important systemic therapy for SLE, but retinal screening is essential.
• Modern HCQ dosing should generally be ≤5 mg/kg/day based on actual body weight.
• The major HCQ toxicity risk factors are high dose, long treatment duration, renal impairment, and tamoxifen use.
• Modern HCQ screening emphasizes OCT plus automated visual fields, with wider pericentral testing particularly important in many Asian patients.
• The old reliance on Amsler grid, color testing, or visible bull’s-eye maculopathy represents late and inadequate screening.
• Vision-threatening retinal vasculitis or choroidopathy requires rapid systemic disease control with rheumatology collaboration.
• The prognosis is generally good for mild ocular disease but can be poor with macular ischemia, severe vaso-occlusion, or optic nerve involvement.