Residency · Residency · Ophthalmology

Ocular Manifestations of Autoimmune and Rheumatologic Disease

Introduction

The eye is frequently affected by systemic autoimmune and rheumatologic diseases. Ocular involvement may be the presenting manifestation, prompting the initial diagnosis, or may develop during the course of known systemic disease. Ophthalmologists play a critical role in recognizing these associations, guiding systemic workup, and collaborating with rheumatologists for optimal management.

Rheumatoid Arthritis

Ocular Manifestations

Keratoconjunctivitis sicca (dry eye): most common ocular finding (up to 25%) Scleritis: 1-6% of RA patients; strongly associated with severe, seropositive disease. Anterior diffuse, anterior nodular, necrotizing (with or without inflammation) Necrotizing scleritis: vision-threatening; thinning with risk of perforation; may indicate systemic vasculitis. Scleromalacia perforans: necrotizing scleritis without inflammation; painless; thinning of sclera with uveal show. Episcleritis: benign; sectoral redness; minimal pain; self-limiting.

Peripheral ulcerative keratitis (PUK): crescent-shaped stromal thinning and ulceration at the peripheral cornea. Associated with systemic vasculitis; requires aggressive systemic immunosuppression. Corneal melt may occur; surgical intervention (tissue adhesive, corneal patch graft) may be needed. Keratitis: corneal melt from inflammatory infiltrates.

Management Principles

Scleritis and PUK require systemic immunosuppression (not just topical treatment) NSAIDs for non-necrotizing scleritis; systemic corticosteroids and immunomodulatory therapy for necrotizing scleritis. Rheumatology co-management essential.

Juvenile Idiopathic Arthritis (JIA)

Uveitis Association

Chronic anterior uveitis: most common extra-articular manifestation; occurs in 10-20% of JIA. Highest risk: oligoarticular JIA, ANA-positive, young girls. Characteristically asymptomatic ("white and quiet" eye); detected only by screening. Complications: band keratopathy, posterior synechiae, cataract, glaucoma, CME, amblyopia.

Screening Guidelines (AAO/AAP)

ANA-positive, oligoarticular, age < 7 at onset: slit-lamp exam every 3 months for first 4 years. Lower-risk categories: every 6-12 months. Continue screening for at least 4 years after disease onset (highest risk period)

Treatment

Topical corticosteroids (prednisolone acetate) for acute inflammation. Methotrexate: first-line steroid-sparing agent. Adalimumab: biologic of choice for refractory JIA-associated uveitis (SYCAMORE trial) Avoid infliximab in children (higher risk of reactions); adalimumab preferred.

Autoimmune Diseases and Key Ocular Manifestations

Systemic Lupus Erythematosus (SLE)

Ocular Manifestations

Dry eye: common (secondary Sjogren syndrome overlap) Retinal vasculitis: cotton-wool spots, retinal hemorrhages, vascular occlusion. Lupus choroidopathy: serous retinal detachment from choroidal vasculitis (active disease marker) Optic neuropathy: ischemic or inflammatory; associated with antiphospholipid antibodies. Scleritis and episcleritis: less common than in RA. Hydroxychloroquine retinal toxicity: iatrogenic; bull's-eye maculopathy from chronic drug use.

Hydroxychloroquine Screening (AAO Guidelines 2016)

Baseline exam within the first year of starting therapy. Annual screening beginning at 5 years of use (earlier if risk factors present) Risk factors for toxicity: daily dose > 5 mg/kg actual body weight, renal impairment, tamoxifen use, pre-existing macular disease. Preferred screening tests: OCT (loss of parafoveal photoreceptor layer) and multifocal ERG (paracentral response depression) 10-2 visual field: white target; paracentral scotomas. Fundus autofluorescence: parafoveal hyperautofluorescent ring (early) or hypoautofluorescent ring (advanced)

Stop drug at first sign of toxicity; damage may progress even after cessation.

Sjogren Syndrome

Ocular Features

Keratoconjunctivitis sicca: hallmark feature; aqueous-deficient dry eye. Rose bengal or lissamine green staining of conjunctiva and cornea. Reduced Schirmer test values (< 5 mm in 5 minutes) Reduced tear break-up time (< 10 seconds) Filamentary keratitis in severe cases.

Classification

Primary Sjogren: dry eye + dry mouth without associated connective tissue disease. Secondary Sjogren: dry eye + dry mouth in setting of another autoimmune disease (RA, SLE)

Diagnosis

Anti-Ro (SS-A) and anti-La (SS-B) antibodies. Minor salivary gland biopsy: focal lymphocytic sialadenitis (focus score >= 1) ACR/EULAR classification criteria (2016)

Management

Artificial tears (preservative-free for frequent use) Cyclosporine 0.05% (Restasis) or lifitegrast 5% (Xiidra): anti-inflammatory drops for chronic dry eye. Punctal plugs, moisture chamber glasses, autologous serum tears. Monitor for lymphoma (increased risk in primary Sjogren)

Spondyloarthropathies

Ankylosing Spondylitis

Acute anterior uveitis (AAU): occurs in 25-40% of patients. HLA-B27 positive in > 90% of ankylosing spondylitis patients. Recurrent, alternating, unilateral, non-granulomatous anterior uveitis. Fibrinous reaction common; may develop posterior synechiae rapidly. Treatment: aggressive topical steroids, cycloplegia; periocular or systemic steroids for severe episodes. Sulfasalazine or anti-TNF therapy for frequently recurrent uveitis.

Reactive Arthritis (Formerly Reiter Syndrome)

Classic triad: arthritis, urethritis, conjunctivitis. Conjunctivitis is the most common ocular finding. Anterior uveitis occurs in 12-37%. HLA-B27 association.

Psoriatic Arthritis

Anterior uveitis in 7-18%. Conjunctivitis, dry eye, keratitis.

Inflammatory Bowel Disease

Anterior uveitis (Crohn disease > ulcerative colitis) Episcleritis, scleritis (less common)

Vasculitis

Giant Cell Arteritis (GCA)

Arteritic anterior ischemic optic neuropathy (A-AION): most feared ocular complication. Sudden painless vision loss; chalky white disc edema. ESR, CRP markedly elevated; temporal artery biopsy confirmatory. Immediate high-dose systemic corticosteroids to protect the fellow eye. Central retinal artery occlusion, posterior ischemic optic neuropathy, cranial nerve palsies also occur. Tocilizumab as a steroid-sparing agent (GiACTA trial)

Granulomatosis with Polyangiitis (GPA, Formerly Wegener)

Orbital inflammation (most common ophthalmic manifestation): proptosis, dacryoadenitis. Scleritis (necrotizing), PUK. Nasolacrimal duct obstruction from nasal mucosal disease. Retinal vasculitis (rare) ANCA testing: c-ANCA/PR3 positive in 90% of systemic GPA.

Polyarteritis Nodosa

Retinal vasculitis, scleritis, cranial nerve palsies. Choroidal infarction (Elschnig spots)

Sarcoidosis

Ocular Involvement (25-50% of sarcoidosis patients)

Any type of uveitis: anterior (most common), intermediate, posterior, panuveitis. Granulomatous: mutton-fat keratic precipitates, iris nodules (Koeppe and Busacca) Periphlebitis with "candle-wax drippings". Lacrimal gland enlargement, conjunctival granulomas (biopsy target) Optic disc granuloma, optic neuropathy. Orbital disease, cranial nerve palsies.

Diagnostic Criteria (International Workshop on Ocular Sarcoidosis)

Seven intraocular signs suggestive of sarcoidosis. Three levels of certainty: definite, presumed, probable (based on biopsy + clinical findings)

Behcet Disease

Occlusive retinal vasculitis (arteritis + phlebitis); most sight-threatening feature. Recurrent hypopyon uveitis. Oral and genital ulceration, skin lesions. HLA-B51 association. Treatment: early immunomodulatory therapy (anti-TNF agents); corticosteroids alone insufficient.

Key Clinical Pearls

JIA-associated uveitis is characteristically asymptomatic in children; screening slit-lamp examinations per AAO/AAP guidelines are essential to prevent amblyopia and structural damage. Hydroxychloroquine retinal toxicity screening should include OCT and visual field testing annually after 5 years of use, with toxicity risk increasing at doses above 5 mg/kg actual body weight. Necrotizing scleritis and peripheral ulcerative keratitis in rheumatoid arthritis signal systemic vasculitis and require urgent systemic immunosuppression, not just topical therapy. Giant cell arteritis requires immediate high-dose systemic corticosteroids; delay risks permanent bilateral vision loss.

References

1. Rosenbaum JT. Uveitis: etiology, clinical manifestations, and diagnosis. UpToDate. 2024.
2. Marmor MF, Kellner U, Lai TY, et al. Recommendations on screening for chloroquine and hydroxychloroquine retinopathy (2016 revision). Ophthalmology. 2016;123(6):1386-1394.
3. Heiligenhaus A, Minden K, Tappeiner C, et al. Update on the ophthalmology of juvenile idiopathic arthritis-associated uveitis. Semin Arthritis Rheum. 2019;49(3):412-418.
4. Seve P, Cacoub P, Bodaghi B, et al. Uveitis in adults: what do rheumatologists need to know? Joint Bone Spine. 2017;84(4):397-402.

For the intern

At 3am, your immediate concerns are acute vision loss, necrotizing scleritis with threatened perforation, hypopyon uveitis suggesting Behçet disease, and suspected giant cell arteritis (GCA). For GCA with sudden vision loss, start high-dose intravenous methylprednisolone immediately to protect the fellow eye—do not wait for biopsy. Necrotizing scleritis requires urgent ophthalmology consultation and systemic immunosuppression. Most other presentations—chronic uveitis screening for juvenile idiopathic arthritis (JIA), dry eye from Sjögren syndrome, hydroxychloroquine toxicity screening—are outpatient issues that can wait until morning rounds.

Common pitfalls

• Missing asymptomatic JIA uveitis: Children with oligoarticular JIA, especially antinuclear antibody (ANA)-positive girls under age seven, need slit-lamp screening every three months even without symptoms. Silent uveitis causes band keratopathy, glaucoma, and blindness.

• Treating scleritis or peripheral ulcerative keratitis (PUK) with topical steroids alone: These conditions reflect systemic vasculitis and require systemic immunosuppression. Topical therapy is insufficient and delays appropriate rheumatology co-management.

• Delaying steroids in suspected GCA: Do not wait for temporal artery biopsy results. Biopsy remains positive for weeks after starting corticosteroids, but untreated arteritic anterior ischemic optic neuropathy (A-AION) quickly causes irreversible fellow-eye blindness.

• Forgetting hydroxychloroquine screening: Annual screening begins at five years of use (earlier with risk factors). Use optical coherence tomography (OCT) and multifocal electroretinogram (ERG) to detect parafoveal photoreceptor damage before bull's-eye maculopathy appears.

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