Rheumatoid Arthritis and the Eye

Rheumatoid arthritis is a chronic symmetric inflammatory polyarthritis that affects the eye through the immune mediated destruction of the lacrimal gland, scleral and corneal collagen and through vasculitis of the limbal and episcleral circulation. Drug treatment adds its own ocular toxicities.

• Dry eye is the commonest ocular manifestation (15 to 25 percent have secondary Sjogren syndrome). Scleritis, and peripheral ulcerative keratitis are rarer but sight threatening.
• Necrotising scleritis and peripheral ulcerative keratitis signal active systemic vasculitis. Untreated, a substantial proportion of patients with these eye signs die within 5 years from vasculitis, so an ocular finding should prompt immediate systemic escalation.
• Uveitis is not a typical feature of rheumatoid arthritis in adults, and its presence should prompt a search for another cause.

• Keratoconjunctivitis sicca: gritty burning eyes, worse in the evening, reduced tear meniscus, filamentary keratitis, punctate epithelial erosions, shortened tear break up time, reduced Schirmer test (under 5 mm in 5 minutes).
• Episcleritis: sectoral or diffuse redness with mild discomfort, blanching with topical phenylephrine 2.5%, self-limiting over 1 to 3 weeks.
• Anterior scleritis: severe boring pain radiating to the face and waking the patient at night, deep violaceous injection, tender globe. Types are diffuse, nodular, necrotising with inflammation, and scleromalacia perforans (necrotising without inflammation, painless, in long standing seropositive disease with scleral thinning showing the uvea through it).
• Posterior scleritis: pain, reduced vision, choroidal folds, exudative retinal detachment, a T sign on B-scan.
• Peripheral ulcerative keratitis: crescent shaped peripheral corneal ulcer with an overhanging edge and stromal infiltrate at the limbus, rapid melt, perforation, associated with limbal vasculitis.
• Marginal (sclerosing) keratitis, central keratolysis, corneal melt in dry eyes, and corneal perforation.
• Systemic stigmata: rheumatoid nodules, deformity of the hands, rheumatoid factor and anti-citrullinated peptide positivity, extra articular disease (lung, vasculitis).
• Drug related: hydroxychloroquine maculopathy (bull's eye), corticosteroid cataract and glaucoma, and rarely ocular surface and optic neuropathy effects of other agents.

• Slit lamp examination, fluorescein staining of cornea and conjunctiva, tear break up time, Schirmer test, lissamine green or rose Bengal staining.
• Scleritis: examination in daylight (violaceous hue), phenylephrine blanching test to separate it from episcleritis, B-scan or anterior segment OCT for scleral thickening, fluorescein angiography for ischaemia (vascular nonperfusion), OCT macula, and corneal topography and pachymetry in keratitis.
• Laboratory: rheumatoid factor, anti-cyclic citrullinated peptide antibody, ESR, CRP, full blood count, anti-nuclear antibody, anti-neutrophil cytoplasmic antibody (to exclude vasculitis), complement, urinalysis and renal function, anti-SSA and SSB if sicca symptoms, and screening for infection (syphilis, tuberculosis) that causes scleritis.
• Corneal scrapings when infection cannot be excluded in a peripheral ulcer.
• Baseline and periodic assessment for hydroxychloroquine retinopathy with OCT, 10-2 automated visual fields (24-2 or 30-2 in Asian patients because of the wider parafoveal pattern), and fundus autofluorescence.

• Dry eye: preservative free artificial tears 4 to 8 times daily, lubricating ointment at bedtime, lid hygiene, punctal occlusion (temporary collagen then permanent silicone plugs), ciclosporin 0.05% twice daily or 0.1% once daily, autologous serum 20% drops 4 to 6 times daily, short courses of loteprednol 0.5% or fluorometholone 0.1% four times daily for flares, bandage or scleral contact lens for persistent epithelial defects, and moisture chamber glasses.
• Episcleritis: lubricants and cool compresses, topical fluorometholone 0.1% four times daily for 1 to 2 weeks, or an oral NSAID short course if needed.
• Diffuse or nodular anterior scleritis: oral NSAID such as flurbiprofen 100 mg three times daily or indomethacin 25 to 50 mg three times daily (or naproxen 500 mg twice daily) with proton pump inhibitor cover. If there is no response within 1 to 2 weeks, oral prednisolone 1 mg/kg/day (maximum 80 mg) tapered over 6 to 8 weeks. Subconjunctival steroid injection is avoided because of the risk of scleral melt. Posterior sub-Tenon triamcinolone 40 mg is an option in unilateral nonnecrotising disease.
• Necrotising scleritis, posterior scleritis and peripheral ulcerative keratitis: urgent systemic immunosuppression with a rheumatology team. Intravenous methylprednisolone 500 to 1000 mg daily for 3 days followed by oral prednisolone 1 mg/kg/day, together with cyclophosphamide 2 mg/kg/day orally or 500 to 1000 mg/m2 intravenously monthly, or rituximab 1000 mg intravenously on days 1 and 15, or adalimumab 40 mg every 2 weeks, or infliximab 5 mg/kg at weeks 0, 2 and 6 then every 8 weeks. Methotrexate 15 to 25 mg weekly or mycophenolate 1 g twice daily is added for maintenance and steroid sparing.
• Peripheral ulcerative keratitis local measures: preservative free lubricants hourly, doxycycline 100 mg twice daily (collagenase inhibition) with oral vitamin C 1 g daily, topical antibiotic cover (such as chloramphenicol 0.5% four times daily or moxifloxacin 0.5% four times daily) when the epithelium is open, bandage lens, conjunctival resection of the adjacent limbal tissue (removes the vascular source of collagenase and immune cells), cyanoacrylate glue for perforations up to 2 mm with a bandage lens, patch graft or tectonic lamellar or penetrating keratoplasty for larger perforations, and hospital admission when the perforation is imminent.
• Surgery in scleritis: scleral patch graft for thinning at risk of perforation, scleral reinforcement, and avoidance of elective surgery until disease is quiet for 3 months.
• Hydroxychloroquine safety: maximum 5 mg/kg/day of real body weight, baseline examination within the first year, then annual screening from year 5 (earlier in renal impairment, tamoxifen use or doses over 5 mg/kg).