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
| Disease | Most Common Ocular Finding | Sight-Threatening Finding | Key Screening/Notes |
|---|---|---|---|
| Rheumatoid arthritis | Dry eye (25%) | Necrotizing scleritis, PUK | Scleritis = systemic vasculitis marker |
| JIA | Chronic anterior uveitis (10-20%) | Band keratopathy, glaucoma, CME | Screen q3mo (ANA+, oligoarticular, age<7) |
| SLE | Dry eye | Retinal vasculitis, lupus choroidopathy | Hydroxychloroquine toxicity screening |
| Sjogren syndrome | KCS (dry eye/mouth) | Corneal melt (rare) | Anti-SSA/Ro; lymphoma risk |
| Granulomatosis with polyangiitis | Orbital inflammation | Necrotizing scleritis, PUK | c-ANCA/PR3; may present as orbital mass |
| Sarcoidosis | Anterior uveitis | Optic neuropathy, retinal vasculitis | ACE, chest CT; any uveitis pattern |
| Ankylosing spondylitis | Acute anterior uveitis | Rare posterior involvement | HLA-B27; recurrent, alternating |
| Behcet disease | Panuveitis with hypopyon | Occlusive retinal vasculitis | Pathergy test; requires IMT |
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
- Rosenbaum JT. Uveitis: etiology, clinical manifestations, and diagnosis. UpToDate. 2024.
- Marmor MF, Kellner U, Lai TY, et al. Recommendations on screening for chloroquine and hydroxychloroquine retinopathy (2016 revision). Ophthalmology. 2016;123(6):1386-1394.
- 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.
- 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.